Pyrazole derivatives and process for the production thereof

ABSTRACT

The present invention provides pyrazole derivatives useful as production intermediates for isoxazoline derivatives having an excellent herbicidal effect and selectivity between crops and weeds as well as processes for producing the same. 
 
The pyrazole derivatives or pharmaceutically acceptable salts thereof which are inventive compounds are represented by the general formula [I] or a salt thereof:  
                 
 
wherein R 1  represents a C1 to C6 alkyl group, R 2  represents a C1 to C3 haloalkyl group, R 3  represents a hydrogen atom, a C1 to C3 alkyl group which may be substituted with one or more substituents selected from the following substituent group α, or a formyl group, R 4  represents a hydrogen atom or a C1 to C3 haloalkyl group, provided that R 4  represents a C1 to C3 haloalkyl group in the case that R 3  is a hydrogen or a formyl group, and R 4  is a hydrogen group or a C1 to C3 haloalkyl group in the case that R 3  is a C1 to C3 alkyl group which may be substituted with one or more substituents selected from the following substituent group α.

TECHNICAL FIELD

The present invention relates to pyrazole derivatives useful asproduction intermediates for agrochemicals and medicaments.

BACKGROUND ART

As a process for producing an isoxazoline derivative useful as aherbicide, for example, Japanese Patent Laid-Open No. 308857/2002discloses Production Examples of isoxazoline derivatives having apyrazole ring wherein starting material having an isoxazoline ring isreacted with sodium hydrosulfide hydrate, followed by a reaction with4-bromomethyl-5-chloro-1-phenyl-3-trifluoromethyl-1H-pyrazole in thepresence of potassium carbonate and Rongalit.

An object of the invention is to provide useful production intermediatesfor the above isoxazoline derivatives and processes for production ofthe intermediates.

DISCLOSURE OF THE INVENTION

As a result of the extensive studies for solving the above problems, thepresent inventors have found that the above isoxazoline derivatives canbe produced more efficiently and conveniently by using specific pyrazolederivatives capable of being produced from easily available startingmaterials as production intermediates. Thus, they have realized that thepyrazole derivatives become production intermediates extremely useful inthe production of the above isoxazoline derivatives and hence haveaccomplished the invention.

Namely, the present invention solves the above problems by providing theinventions of the following (1) to (15).

(1) A pyrazole derivative represented by the general formula [I] or asalt thereof:

wherein R¹ represents a C1 to C6 alkyl group, R² represents a C1 to C3haloalkyl group, R³ represents a hydrogen atom, a C1 to C3 alkyl groupwhich may be substituted with one or more substituents selected from thefollowing substituent group α, or a formyl group, R⁴ represents ahydrogen atom or a C1 to C3 haloalkyl group, provided that R⁴ representsa C1 to C3 haloalkyl group in the case that R³ is a hydrogen atom or aformyl group and R is a hydrogen atom or a C1 to C3 haloalkyl group inthe case that R³ is a C1 to C3 alkyl group which may be substituted withone or more substituents selected from the following substituent groupα; “Substituent group α”

-   -   halogen atoms, —SH group, —SC(═NH)NH₂ group

(2) The pyrazole derivative or salt thereof according to (1), wherein R⁴is a C1 to C3 haloalkyl group.

(3) The pyrazole derivative or salt thereof according to (1), wherein R³is a C1 to C3 alkyl group and R⁴ is a hydrogen atom.

(4) The pyrazole derivative or salt thereof according to (1), wherein R³is a methyl group which may be substituted with one or more substituentsselected from the substituent group α.

(5) The pyrazole derivative or salt thereof according to (3), wherein R³is a methyl group.

(6) A process for producing a pyrazole derivative represented by thegeneral formula [3], comprising a step of reacting a compoundrepresented by the general formula [1] with a compound represented bythe general formula [2]:

wherein R¹ and R² represent the same meanings as mentioned above, R⁵represents a C1 to C3 alkyl group, a phenyl group which may besubstituted, or a benzyl group which may be substituted, and R⁶ is a C1to C3 alkyl group.

(7) A process for producing a pyrazole derivative represented by thegeneral formula [6], comprising a step of reacting a compoundrepresented by the general formula [4] with a compound represented bythe general formula [5] in the presence of a base:

wherein R¹, R², R⁴, and R⁶ represent the same meanings as mentionedabove, and L¹ is a leaving group which is more reactive than a halogenatom remaining after haloalkylation and represents a halogen atom, a C1to C3 alkylsulfonyloxy group, a C1 to C3 haloalkylsulfonyloxy group, aphenylsulfonyloxy group which may be substituted, or a benzylsulfonyloxygroup which may be substituted, and the like.

(8) A process for producing a pyrazole derivative represented by thegeneral formula [6], comprising a step of reacting a compoundrepresented by the general formula [4] with triphenylphosphine, acompound represented by the general formula [7], and an azo compound[8]:

wherein R¹, R², R⁴, and R⁶ represent the same meanings as mentionedabove.

(9) A process for producing a pyrazole derivative represented by thegeneral formula [10], comprising a step of reacting a compoundrepresented by the general formula [9] with a halogenating agent:

wherein R¹, R², and R⁴ represent the same meanings as mentioned above,R⁷ and R⁸ each represents a hydrogen atom or a C1 to C2 alkyl group, andX is a halogen atom.

(10) A process for producing a pyrazole derivative represented by thegeneral formula [12], comprising a step of reacting a compoundrepresented by the general formula [10] with a compound represented bythe general formula [11]:

wherein R¹, R², R⁴, R⁷, R⁸, and X represent the same meanings asmentioned above.

(11) The process for producing a pyrazole derivative represented by thegeneral formula [13], wherein the compound represented by the generalformula [12] according to the above (10) is hydrolyzed.

(12) The process for producing a pyrazole derivative represented by thegeneral formula [13], wherein the compound represented by the generalformula [10] according to the above (10) is reacted with a sulfide.

(13) A process for producing a pyrazole derivative -represented by thegeneral formula [15], comprising a step of formylating a compoundrepresented by the general formula [14]:

wherein R¹ and R² represent the same meanings as mentioned above.

(14) A process for producing a pyrazole derivative represented by thegeneral formula [17], comprising a step of reacting a compoundrepresented by the general formula [16] with a compound represented bythe general formula [5] in the presence of a base:

wherein R¹, R², R⁴, and L¹ represent the same meanings as mentionedabove.

(15) A process for producing a pyrazole derivative represented by thegeneral formula [19], comprising a step of halomethylating a compoundrepresented by the general formula [18]:

wherein R¹, R², R⁴, and X represent the same meanings as mentionedabove.

Incidentally, the definitions of the terms used in the presentspecification are given below.

The expression of “C1 to C6” and the like indicates that a substituentappearing after the expression has 1 to 6 carbon atoms in the case of“C1 to C6”.

The halogen atom refers to a fluorine atom, a chlorine atom, a bromineatom, or an iodine atom.

The C1 to C3 alkyl group refers, unless otherwise specified, to a linearor branched alkyl group having 1 to 3 carbon atoms, and examples thereofinclude a methyl group, an ethyl group, an n-propyl group, an iso-propylgroup, and the like.

The C1 to C6 alkyl group refers, unless otherwise specified, to a linearor branched alkyl group having 1 to 6 carbon atoms, and examples thereofinclude a methyl group, an ethyl group, an n-propyl group, an iso-propylgroup, an n-butyl group, an isobutyl group, a sec-butyl group, atert-butyl group, an n-pentyl group, an iso-pentyl group, a neopentylgroup, an n-hexyl group, an iso-hexyl group, a 3,3-dimethylbutyl group,and the like.

The C1 to C3 haloalkyl group refers, unless otherwise specified, to alinear or branched alkyl group having 1 to 3 carbon atoms, which issubstituted with 1 to 7 halogen atoms which are the same or differentfrom one another, and examples thereof include a fluoromethyl group, achloromethyl group, a bromomethyl group, a difluoromethyl group, atrifluoromethyl group, a dichlorofluoromethyl group, achlorodifluoromethyl group, a 2,2-difluoroethyl group, a2,2,2-trifluoroethyl group, a pentafluoroethyl group, a1-fluoro-1-methylethyl group, a 1-trifluoromethyl-2,2,2-trifluoroethylgroup, and the like.

The C1 to C4 alkylsulfonyloxy group refers to a (C1 to C4 alkyl)-SO₂—O—group wherein the alkyl moiety represents the same meaning as mentionedabove, and examples thereof include a methanesulfonyloxy group, anethanesulfonyloxy group, and the like.

The C1 to C3 haloalkylsulfonyloxy group refers to a (C1 to C3haloalkyl)-SO₂—O— group wherein the haloalkyl moiety represents the samemeaning as mentioned above, and examples thereof include atrifluoromethanesulfonyloxy group, a trichloromethanesulfonyloxy group,and the like.

The “group which may be substituted” in the phenyl group (which may besubstituted), the phenylsulfonyloxy group (which may be substituted),the benzyl group (which may be substituted), or the benzylsulfonyloxygroup (which may be substituted) refers to a group which may besubstituted with, for example, a halogen atom, a C1 to C10 alkyl group,a C1 to C4 haloalkyl group, a C1 to C10 alkoxyalkyl group, a C1 to C10alkoxy group, a C1 to C10 alkylthio group, a C1 to C10 alkylsulfonylgroup, an acyl group, a C1 to C10 alkoxycarbonyl group, a cyano group, acarbamoyl group (a nitrogen atom thereof may be substituted with C1 toC10 alkyl groups which are the same or different from each other), anitro group, or an amino group (a nitrogen atom thereof may besubstituted with C1 to C10 alkyl groups, C1 to C6 acyl groups, C1 to C4haloalkylcarbonyl groups, C1 to C10 alkylsulfonyl groups, and C1 to C4haloalkylsulfonyl groups, which are the same or different from eachother).

The salt is a salt of a compound of the general formula [I] wherein ahydroxyl group, an —SH group, an —SC(═NH)NH₂ group, or the like ispresent in the structure, with a metal or an organic base or with amineral acid or an organic acid. The metal in this case includes alkalimetals such as sodium and potassium and alkaline earth metals such asmagnesium and calcium. The organic base includes triethylamine anddiisopropylamine. The mineral acid includes hydrochloric acid,hydrobromic acid, sulfuric acid, and the like. The organic acid includesacetic acid, methanesulfonic acid, p-toluenesulfonic acid, and the like.

BEST MODE FOR CARRYING OUT THE INVENTION

Next, representative examples of the pyrazole derivatives represented bythe general formula [I] or salt thereof (the inventive compounds) areshown in Tables 1 to 11. However, the compounds of the present inventionare not restricted to these examples.

The following representations in the tables in the present specificationrepresent the respective corresponding groups as shown below.

-   -   Me: methyl group    -   Et: ethyl group    -   Pr-n: n-propyl group    -   Pr-i: iso-propyl group    -   Bu-n: n-butyl group    -   Bu-i: iso-butyl group    -   Bu-s: sec-butyl group    -   Bu-t: tert-butyl group    -   Pen-n: n-pentyl group    -   Hex-n: n-hexyl group

When the compound of the present invention contains a hydroxyl group asa substituent, there may exist compounds having keto-enol tautomers. Anyof the tautomers and any mixtures thereof are included in the compoundsof the present invention. TABLE 1 [I]

Compound No. R¹ R² R³ R⁴ 001 Me CF₃ H CHF₂ 002 Me CF₃ H CH₂CHF₂ 003 MeCF₃ H CH₂CF₃ 004 Me CHF₂ H CHF₂ 005 Me CHF₂ H CH₂CHF₂ 006 Me CHF₂ HCH₂CF₃ 007 Me CClF₂ H CHF₂ 008 Me CClF₂ H CH₂CHF₂ 009 Et CF₃ H CHF₂ 010Et CF₃ H CH₂CHF₂ 011 Et CF₃ H CH₂CF₃

TABLE 2 Compound No. R¹ R² R³ R⁴ 012 Et CHF₂ H CHF₂ 013 Et CHF₂ HCH₂CHF₂ 014 Et CHF₂ H CH₂CF₃ 015 Pr-i CF₃ H CHF₂ 016 Pr-i CF₃ H CH₂CHF₂017 Pr-i CF₃ H CH₂CF₃ 018 Pr-n CF₃ H CHF₂ 019 Pr-n CF₃ H CH₂CHF₂ 020Pr-n CF₃ H CH₂CF₃ 021 Bu-t CF₃ H CHF₂ 022 Bu-t CF₃ H CH₂CHF₂ 023 Bu-tCF₃ H CH₂CF₃ 024 Pen-n CF₃ H CHF₂ 025 Hex-n CF₃ H CHF₂ 026 Me CF₃ CHOCHF₂ 027 Me CHF₂ CHO CHF₂ 028 Me CF₃ CHO CH₂CHF₂ 029 Me CF₃ CHO CH₂CF₃030 Et CF₃ CHO CHF₂ 031 Et CF₃ CHO CH₂CHF₂ 032 Pr-i CF₃ CHO CHF₂ 033Pr-i CF₃ CHO CH₂CHF₂ 034 Bu-t CF₃ CHO CHF₂ 035 Bu-t CF₃ CHO CH₂CHF₂

TABLE 3

Compound No. R¹ R² R³ R⁴ 036 Me CF₃ Me H 037 Et CF₃ Me H 038 Pr-i CF₃ MeH 039 Pr-n CF₃ Me H 040 Bu-n CF₃ Me H 041 Bu-s CF₃ Me H 042 Bu-i CF₃ MeH 043 Bu-t CF₃ Me H 044 Pen-n CF₃ Me H 045 Hex-n CF₃ Me H 046 Me CHF₂ MeH 047 Et CHF₂ Me H 048 Pr-i CHF₂ Me H 049 Pr-n CHF₂ Me H 050 Bu-n CHF₂Me H 051 Bu-s CHF₂ Me H 052 Bu-i CHF₂ Me H 053 Bu-t CHF₂ Me H 054 Pen-nCHF₂ Me H 055 Hex-n CHF₂ Me H 056 Me CF₃ Et H 057 Et CF₃ Et H 058 Pr-iCF₃ Et H 059 Pen-n CF₃ Et H 060 Hex-n CF₃ Et H 061 Me CHF₂ Et H 062 EtCHF₂ Et H 063 Pr-i CHF₂ Et H 064 Me CF₃ Pr-n H 065 Et CF₃ Pr-n H 066Pr-i CF₃ Pr-n H

TABLE 4 Compound No. R¹ R² R³ R⁴ 067 Me CHF₂ Pr-n H 068 Et CHF₂ Pr-n H069 Pr-i CHF₂ Pr-n H 070 Me CF₃ Pr-i H 071 Et CF₃ Pr-i H 072 Pr-i CF₃Pr-i H 073 Me CHF₂ Pr-i H 074 Et CHF₂ Pr-i H 075 Pr-i CHF₂ Pr-i H 076 MeCF₃ Me CHF₂ 077 Me CHF₂ Me CHF₂ 078 Me CF₃ Me CH₂CHF₂ 079 Me CF₃ MeCH₂CF₃ 080 Et CF₃ Me CHF₂ 081 Et CHF₂ Me CHF₂ 082 Et CF₃ Me CH₂CHF₂ 083Et CF₃ Me CH₂CF₃ 084 Pr-i CF₃ Me CHF₂ 085 Pr-i CHF₂ Me CHF₂ 086 Pr-i CF₃Me CH₂CHF₂ 087 Pr-i CF₃ Me CH₂CF₃ 088 Pr-n CF₃ Me CHF₂ 089 Pr-n CF₃ MeCH₂CHF₂ 090 Pr-n CF₃ Me CH₂CF₃ 091 Bu-n CF₃ Me CHF₂ 092 Bu-n CF₃ MeCH₂CHF₂ 093 Bu-n CF₃ Me CH₂CF₃ 094 Bu-i CF₃ Me CHF₂ 095 Bu-i CF₃ MeCH₂CHF₂ 096 Bu-i CF₃ Me CH₂CF₃ 097 Bu-s CF₃ Me CHF₂ 098 Bu-s CF₃ MeCH₂CHF₂ 099 Bu-s CF₃ Me CH₂CF₃ 100 Bu-t CF₃ Me CHF₂ 101 Bu-t CF₃ MeCH₂CHF₂

TABLE 5 Compound No. R¹ R² R³ R⁴ 102 Bu-t CF₃ Me CH₂CF₃ 103 Pen-n CF₃ MeCHF₂ 104 Hex-n CF₃ Me CHF₂ 105 Me CF₃ Et CHF₂ 106 Me CF₃ Et CH₂CHF₂ 107Et CF₃ Et CHF₂ 108 Et CF₃ Et CH₂CHF₂ 109 Pr-i CF₃ Et CHF₂ 110 Pr-i CF₃Et CH₂CHF₂ 111 Me CF₃ Pr-n CHF₂ 112 Me CF₃ Pr-n CH₂CHF₂ 113 Et CF₃ Pr-nCHF₂ 114 Et CF₃ Pr-n CH₂CHF₂ 115 Pr-i CF₃ Pr-n CHF₂ 116 Pr-i CF₃ Pr-nCH₂CHF₂ 117 Me CF₃ Pr-i CHF₂ 118 Me CF₃ Pr-i CH₂CHF₂ 119 Et CF₃ Pr-iCHF₂ 120 Et CF₃ Pr-i CH₂CHF₂ 121 Pr-i CF₃ Pr-i CHF₂ 122 Pr-i CF₃ Pr-iCH₂CHF₂ 123 Me CF₃ CH₂Cl CHF₂ 124 Me CHF₂ CH₂Cl CHF₂ 125 Me CF₃ CH₂ClCH₂CHF₂ 126 Me CF₃ CH₂Cl CH₂CF₃ 127 Et CF₃ CH₂Cl CHF₂ 128 Et CF₃ CH₂ClCH₂CHF₂ 129 Et CF₃ CH₂Cl CH₂CF₃ 130 Pr-i CF₃ CH₂Cl CHF₂ 131 Pr-i CF₃CH₂Cl CH₂CHF₂ 132 Pr-i CF₃ CH₂Cl CH₂CF₃ 133 Pr-n CF₃ CH₂Cl CHF₂ 134 Pr-nCF₃ CH₂Cl CH₂CHF₂ 135 Pr-n CF₃ CH₂Cl CH₂CF₃ 136 Bu-n CF₃ CH₂Cl CHF₂

TABLE 6 Compound No. R¹ R² R³ R⁴ 137 Bu-n CF₃ CH₂Cl CH₂CHF₂ 138 Bu-n CF₃CH₂Cl CH₂CF₃ 140 Bu-t CF₃ CH₂Cl CHF₂ 141 Bu-t CF₃ CH₂Cl CH₂CHF₂ 142 Bu-tCF₃ CH₂Cl CH₂CF₃ 143 Me CF₃ CH(Me)Cl CHF₂ 144 Me CHF₂ CH(Me)Cl CHF₂ 145Me CF₃ CH(Me)Cl CH₂CHF₂ 146 Me CF₃ CH(Me)Cl CH₂CF₃ 147 Me CF₃ CH(Et)ClCHF₂ 148 Me CHF₂ CH(Et)Cl CHF₂ 149 Me CF₃ CH(Et)Cl CH₂CHF₂ 150 Me CF₃CH(Et)Cl CH₂CF₃ 151 Me CF₃ CH₂Br CHF₂ 152 Me CHF₂ CH₂Br CHF₂ 153 Me CF₃CH₂Br CH₂CHF₂ 154 Me CF₃ CH₂Br CH₂CF₃ 155 Et CF₃ CH₂Br CHF₂ 156 Et CF₃CH₂Br CH₂CHF₂ 157 Et CF₃ CH₂Br CH₂CF₃ 158 Pr-i CF₃ CH₂Br CHF₂ 159 Pr-iCF₃ CH₂Br CH₂CHF₂ 160 Pr-i CF₃ CH₂Br CH₂CF₃ 161 Pr-n CF₃ CH₂Br CHF₂ 162Pr-n CF₃ CH₂Br CH₂CHF₂ 163 Pr-n CF₃ CH₂Br CH₂CF₃ 164 Bu-n CF₃ CH₂Br CHF₂165 Bu-n CF₃ CH₂Br CH₂CHF₂ 166 Bu-n CF₃ CH₂Br CH₂CF₃ 167 Bu-t CF₃ CH₂BrCHF₂ 168 Bu-t CF₃ CH₂Br CH₂CHF₂ 169 Bu-t CF₃ CH₂Br CH₂CF₃ 170 Me CF₃CH(Me)Br CHF₂ 171 Me CHF₂ CH(Me)Br CHF₂ 172 Me CF₃ CH(Me)Br CH₂CHF₂

TABLE 7 Compound No. R¹ R² R³ R⁴ 173 Me CF₃ CH(Me)Br CH₂CF₃ 174 Me CF₃CH(Et)Br CHF₂ 175 Me CHF₂ CH(Et)Br CHF₂ 176 Me CF₃ CH(Et)Br CH₂CHF₂ 177Me CF₃ CH(Et)Br CH₂CF₃ 178 Me CF₃ CH₂SC(═NH)NH₂HCl salt CHF₂ 179 Me CHF₂CH₂SC(═NH)NH₂HCl salt CHF₂ 180 Me CF₃ CH₂SC(═NH)NH₂HCl salt CH₂CHF₂ 181Me CF₃ CH₂SC(═NH)NH₂HCl salt CH₂CF₃ 182 Et CF₃ CH₂SC(═NH)NH₂HCl saltCHF₂ 183 Et CF₃ CH₂SC(═NH)NH₂HCl salt CH₂CHF₂ 184 Et CF₃CH₂SC(═NH)NH₂HCl salt CH₂CF₃ 185 Pr-i CF₃ CH₂SC(═NH)NH₂HCl salt CHF₂ 186Pr-i CF₃ CH₂SC(═NH)NH₂HCl salt CH₂CHF₂ 187 Pr-i CF₃ CH₂SC(═NH)NH₂HClsalt CH₂CF₃ 188 Pr-n CF₃ CH₂SC(═NH)NH₂HCl salt CHF₂ 189 Pr-n CF₃CH₂SC(═NH)NH₂HCl salt CH₂CHF₂ 190 Pr-n CF₃ CH₂SC(═NH)NH₂HCl salt CH₂CF₃191 Bu-n CF₃ CH₂SC(═NH)NH₂HCl salt CHF₂ 192 Bu-n CF₃ CH₂SC(═NH)NH₂HClsalt CH₂CHF₂ 193 Bu-n CF₃ CH₂SC(═NH)NH₂HCl salt CH₂CF₃ 194 Bu-t CF₃CH₂SC(═NH)NH₂HCl salt CHF₂ 195 Bu-t CF₃ CH₂SC(═NH)NH₂HCl salt CH₂CHF₂196 Bu-t CF₃ CH₂SC(═NH)NH₂HCl salt CH₂CF₃ 197 Me CF₃ CH₂SC(═NH)NH₂HBrsalt CHF₂ 198 Me CHF₂ CH₂SC(═NH)NH₂HBr salt CHF₂ 199 Me CF₃CH₂SC(═NH)NH₂HBr salt CH₂CHF₂ 200 Me CF₃ CH₂SC(═NH)NH₂HBr salt CH₂CF₃201 Et CF₃ CH₂SC(═NH)NH₂HBr salt CHF₂ 202 Et CF₃ CH₂SC(═NH)NH₂HBr saltCH₂CHF₂ 203 Et CF₃ CH₂SC(═NH)NH₂ HBr salt CH₂CF₃ 204 Pr-i CF₃CH₂SC(═NH)NH₂HBr salt CHF₂ 205 Pr-i CF₃ CH₂SC(═NH)NH₂HBr salt CH₂CHF₂206 Pr-i CF₃ CH₂SC(═NH)NH₂HBr salt CH₂CF₃ 207 Pr-n CF₃ CH₂SC(═NH)NH₂HBrsalt CHF₂

TABLE 8 Compound No. R¹ R² R³ R⁴ 208 Pr-n CF₃ CH₂SC(═NH)NH₂HBr saltCH₂CHF₂ 209 Pr-n CF₃ CH₂SC(═NH)NH₂HBr salt CH₂CF₃ 210 Bu-n CF₃CH₂SC(═NH)NH₂HBr salt CHF₂ 211 Bu-n CF₃ CH₂SC(═NH)NH₂HBr salt CH₂CHF₂212 Bu-n CF₃ CH₂SC(═NH)NH₂HBr salt CH₂CF₃ 213 Bu-t CF₃ CH₂SC(═NH)NH₂HBrsalt CHF₂ 214 Bu-t CF₃ CH₂SC(═NH)NH₂HBr salt CH₂CHF₂ 215 Bu-t CF₃CH₂SC(═NH)NH₂HBr salt CH₂CF₃ 216 Me CF₃ CH₂SH CHF₂ 217 Me CHF₂ CH₂SHCHF₂ 218 Me CF₃ CH₂SH CH₂CHF₂ 219 Me CF₃ CH₂SH CH₂CF₃ 220 Et CF₃ CH₂SHCHF₂ 221 Et CF₃ CH₂SH CH₂CHF₂ 222 Et CF₃ CH₂SH CH₂CF₃ 223 Pr-i CF₃ CH₂SHCHF₂ 224 Pr-i CF₃ CH₂SH CH₂CHF₂ 225 Pr-i CF₃ CH₂SH CH₂CF₃ 226 Pr-n CF₃CH₂SH CHF₂ 227 Pr-n CF₃ CH₂SH CH₂CHF₂ 228 Pr-n CF₃ CH₂SH CH₂CF₃ 229 Bu-nCF₃ CH₂SH CHF₂ 230 Bu-n CF₃ CH₂SH CH₂CHF₂ 231 Bu-n CF₃ CH₂SH CH₂CF₃ 232Bu-t CF₃ CH₂SH CHF₂ 233 Bu-t CF₃ CH₂SH CH₂CHF₂ 234 Bu-t CF₃ CH₂SH CH₂CF₃235 Me CF₃ CH(Me)SH CHF₂ 236 Me CHF₂ CH(Me)SH CHF₂ 237 Me CF₃ CH(Me)SHCH₂CHF₂ 238 Me CF₃ CH(Me)SH CH₂CF₃ 239 Me CF₃ CH(Et)SH CHF₂ 240 Me CHF₂CH(Et)SH CHF₂ 241 Me CF₃ CH(Et)SH CH₂CHF₂ 242 Me CF₃ CH(Et)SH CH₂CF₃

TABLE 9 Compound No. R¹ R² R³ R⁴ 243 Me CF₃ CH₂S⁻Na⁺ salt CHF₂ 244 MeCHF₂ CH₂S⁻Na⁺ salt CHF₂ 245 Me CF₃ CH₂S⁻Na⁺ salt CH₂CHF₂ 246 Me CF₃CH₂S⁻Na⁺ salt CH₂CF₃ 247 Et CF₃ CH₂S⁻Na⁺ salt CHF₂ 248 Et CF₃ CH₂S⁻Na⁺salt CH₂CHF₂ 249 Et CF₃ CH₂S⁻Na⁺ salt CH₂CF₃ 250 Pr-i CF₃ CH₂S⁻Na⁺ saltCHF₂ 251 Pr-i CF₃ CH₂S⁻Na⁺ salt CH₂CHF₂ 252 Pr-i CF₃ CH₂S⁻Na⁺ saltCH₂CF₃ 253 Pr-n CF₃ CH₂S⁻Na⁺ salt CHF₂ 254 Pr-n CF₃ CH₂S⁻Na⁺ saltCH₂CHF₂ 255 Pr-n CF₃ CH₂S⁻Na⁺ salt CH₂CF₃ 256 Bu-n CF₃ CH₂S⁻Na⁺ saltCHF₂ 257 Bu-n CF₃ CH₂S⁻Na⁺ salt CH₂CHF₂ 258 Bu-n CF₃ CH₂S⁻Na⁺ saltCH₂CF₃ 259 Bu-t CF₃ CH₂S⁻Na⁺ salt CHF₂ 260 Bu-t CF₃ CH₂S⁻Na⁺ saltCH₂CHF₂ 261 Bu-t CF₃ CH₂S⁻Na⁺ salt CH₂CF₃ 262 Me CF₃ CH₂S⁻K⁺ salt CHF₂263 Me CHF₂ CH₂S⁻K⁺ salt CHF₂ 264 Me CF₃ CH₂S⁻K⁺ salt CH₂CHF₂ 265 Me CF₃CH₂S⁻K⁺ salt CH₂CF₃ 266 Et CF₃ CH₂S⁻K⁺ salt CHF₂ 267 Et CF₃ CH₂S⁻K⁺ saltCH₂CHF₂ 268 Et CF₃ CH₂S⁻K⁺ salt CH₂CF₃ 269 Pr-i CF₃ CH₂S⁻K⁺ salt CHF₂270 Pr-i CF₃ CH₂S⁻K⁺ salt CH₂CHF₂ 271 Pr-i CF₃ CH₂S⁻K⁺ salt CH₂CF₃ 272Pr-n CF₃ CH₂S⁻K⁺ salt CHF₂ 273 Pr-n CF₃ CH₂S⁻K⁺ salt CH₂CHF₂ 274 Pr-nCF₃ CH₂S⁻K⁺ salt CH₂CF₃ 275 Bu-n CF₃ CH₂S⁻K⁺ salt CHF₂ 276 Bu-n CF₃CH₂S⁻K⁺ salt CH₂CHF₂ 277 Bu-n CF₃ CH₂S⁻K⁺ salt CH₂CF₃

TABLE 10 Compound No. R¹ R² R³ R⁴ 278 Bu-t CF₃ CH₂S⁻K⁺ salt CHF₂ 279Bu-t CF₃ CH₂S⁻K⁺ salt CH₂CHF₂ 280 Bu-t CF₃ CH₂S⁻K⁺ salt CH₂CF₃

TABLE 11

Compound No. R¹ R² R³ 281 Me CF₃ CHO 282 Et CF₃ CHO 283 Pr-i CF₃ CHO 284Pr-n CF₃ CHO 285 Bu-n CF₃ CHO 286 Bu-s CF₃ CHO 287 Bu-i CF₃ CHO 288 Bu-tCF₃ CHO 289 Pen-n CF₃ CHO 290 Hex-n CF₃ CHO 291 Me CHF₂ CHO 292 Et CHF₂CHO 293 Pr-i CHF₂ CHO 294 Bu-t CHF₂ CHO 295 Pen-n CHF₂ CHO 296 Hex-nCHF₂ CHO

The inventive compounds represented by the general formula [I] can beproduced, for example, by the following production processes, but theprocess for producing the same is not restricted to such processes.

The following will describe each of the production processes in detail.

wherein R¹ and R² represent the same meanings as mentioned above, R⁵represents a C1 to C3 alkyl group, a phenyl group which may besubstituted, or a benzyl group which may be substituted, and R⁶ is a C1to C3 alkyl group.(Step 1)

A compound represented by the general formula [3] can be produced byreacting the compound represented by the general formula [1] with thecompound represented by the general formula [2] in a solvent or in theabsence of a solvent (preferably in a suitable solvent) in the presenceor absence of an acid catalyst.

With respect to the reaction temperature, all the reactions areconducted at any temperature of −50° C. to a reflux temperature of thereaction system, preferably in the temperature range of −20° C. to 100°C. and the reaction may be completed within a period of 0.5 hour to 72hours, although the period varies depending on the compounds.

With respect to the amounts of the reagents to be used in the reaction,the amount of the compound represented by the general formula [2] is 1to 3 equivalents and, when an acid catalyst is used, the amount of theacid catalyst when used is 0.01 to 2 equivalents, all relative to 1equivalent of the compound represented by the general formula [1].

Examples of the solvent include ethers such as dioxane, tetrahydrofuran,and dimethoxyethane; halogenated hydrocarbons such as dichloroethane,carbon tetrachloride, chlorobenzene, and dichlorobenzene; amides such asN,N-dimethylacetamide, N,N-dimethylformamide, andN-methyl-2-pyrrolidinone; sulfur compounds such as dimethyl sulfoxideand sulfolane; aromatic hydrocarbons such as benzene, toluene, andxylene; alcohols such as methanol, ethanol, n-propanol, 2-propanol,n-butanol, and 2-methyl-2-propanol; carboxylic acids such as formic acidand acetic acid; water; and mixtures thereof. The amount of the solventto be used is in a ratio of 0.1 to 20 liters, preferably 0.1 to 5 litersof the solvent to 1 mol of the compound represented by the generalformula [1].

Examples of the acid catalyst include mineral acids such as hydrochloricacid, hydrobromic acid, and sulfuric acid; and organic acids such asformic acid, acetic acid, methanesulfonic acid, and p-toluenesulfonicacid.

wherein R¹, R², R⁴, and R⁶ represent the same meanings as mentionedabove, and L¹ is a leaving group which is more reactive than a halogenatom remaining after haloalkylation and represents a halogen atom, a C1to C3 alkylsulfonyloxy group, a C1 to C3 haloalkylsulfonyloxy group, aphenylsulfonyloxy group which may be substituted, a benzylsulfonyloxygroup which may be substituted, or the like and, for example, itrepresents a chlorine atom or a bromine atom when R⁴ is a CHF₂ group andrepresents a chlorine atom, a bromine atom, an iodine atom, ap-toluenesulfonyloxy group, a trifluoromethanesulfonyloxy group, amethanesulfonyloxy group, or the like when R⁴ is a CH₂CF₃ group.(Step 2)

A compound represented by the general formula [6] can be produced byreacting the compound represented by the general formula [4] with thecompound represented by the general formula [5] in a solvent or in theabsence of a solvent (preferably in a suitable solvent) in the presenceor absence of a catalyst in the presence of a base.

With respect to the reaction temperature, all the reactions areconducted at any temperature of 0° C. to a reflux temperature of thereaction system, preferably in the temperature range of 0° C. to 100° C.and the reaction may be completed within a period of 0.5 hour to 24hours, although the period varies depending on the compounds.

With respect to the amounts of the reagents to be used in the reaction,the amount of the compound represented by the general formula [5] is 1to 5 equivalents, preferably 1 to 3 equivalents, the amount of the baseis 1 to 20 equivalents, preferably 1 to 10 equivalents, and the amountof the catalyst is 0.01 to 2.0 equivalents, preferably 0.01 to 0.5equivalent, all relative to 1 equivalent of the compound represented bythe general formula [4].

Examples of the base include alkali metal carbonates such as sodiumcarbonate and potassium carbonate; alkali metal bicarbonates such assodium hydrogen carbonate and potassium hydrogen carbonate; alkali metalhydroxides such as sodium hydroxide and potassium hydroxide; alkalimetal hydrides such as potassium hydride and sodium hydride; alkalimetal alcoholates such as sodium ethoxide and sodium methoxide; andorganic bases such as 1,8-diazabicyclo[5.4.0]-7-undecene, triethylamine,and pyridine.

Examples of the solvent include ethers such as dioxane, tetrahydrofuran,and 1,2-dimethoxyethane; halogenated hydrocarbons such asdichloroethane, carbon tetrachloride, chlorobenzene, anddichlorobenzene; amides such as N,N-dimethylacetamide,N,N-dimethylformamide, and N-methyl-2-pyrrolidinone; sulfur compoundssuch as dimethyl sulfoxide and sulfolane; aromatic hydrocarbons such asbenzene, toluene, and xylene; alcohols such as methanol, ethanol,n-propanol, 2-propanol, n-butanol, and 2-methyl-2-propanol; ketones suchas acetone and methyl ethyl ketone; nitrites such as acetonitrile;water; and mixtures thereof. The amount of the solvent to be used is ina ratio of 0.1 to 20 liters, preferably 0.1 to 5 liters of the solventto 1 mol of the compound represented by the general formula [4].

Examples of the catalyst include crown ethers such as 18-crown-6 and15-crown-5; quaternary ammonium salts such as tetra-n-butylammoniumbromide and benzyltrimethylammonium bromide; and quaternary phosphoniumsalts such as tetra-n-butylphosphoniumm bromide.

wherein R¹, R², R⁴, and R⁶ represent the same meanings as mentionedabove.(Step 3)

A compound represented by the general formula [6] can be produced byreacting the compound represented by the general formula [4] with thecompound represented by the general formula [7] in the presence of anazo compound [8] and triphenylphosphine in a solvent, in accordance withthe method described in Synthesis, 1981, 1-28.

This reaction is conducted ordinarily at a reaction temperature of −30to 100° C. for 10 minutes to 24 hours.

With respect to the amounts of the reagents to be used in the reaction,it is desired that the amount of the compound represented by the generalformula [7] is 1 to 1.5 equivalents, the amount of the azo compound [8]is 1 to 1.5 equivalents, and the amount of triphenylphosphine is 1 to1.5 equivalents, all relative to 1 equivalent of the compoundrepresented by the general formula [4], but these amounts can beoptionally varied depending upon the conditions of the reaction.

Examples of the solvent include ethers such as dioxane andtetrahydrofuran; halogenated hydrocarbons such as 1,2-dichloroethane,carbon tetrachloride, chlorobenzene, and dichlorobenzene; amides such asN,N-dimethylacetamide, N,N-dimethylformamide, andN-methyl-2-pyrrolidinone; sulfur compounds such as dimethyl sulfoxideand sulfolane; aromatic hydrocarbons such as benzene, toluene, andxylene; nitrites such as acetonitrile; and mixtures thereof. The amountof the solvent to be used is in a ratio of 0.1 to 20 liters, preferably0.1 to 5 liters of the solvent to 1 mol of the compound represented bythe general formula [4].

Examples of the azo compound [8] include diethyl azodicarboxylate,diisopropyl azodicarboxylate, and the like.

wherein R¹, R², and R⁴ represent the same meanings as mentioned above,R⁷ and R⁸ each represents a hydrogen atom or a C1 to C3 alkyl group, andX is a halogen atom.(Step 4)

The compound represented by the general formula [10] can be produced byreacting the compound represented by the general formula [9] with ahalogenating agent in a solvent in the presence or absence of acatalyst. In this step, the reaction may be conducted under lightirradiation. Furthermore, in order to trap an acid produced as aby-product, the reaction may be conducted in the presence of a base.

This reaction is conducted ordinarily at a reaction temperature of 20 to150° C. for 10 minutes to 48 hours.

With respect to the amounts of the reagents to be used, the amount ofthe halogenating agent is desirably 1 to 10 equivalents relative to 1equivalent of the compound of the general formula [9] but it can beoptionally varied depending upon the conditions of the reaction. Theamount of the catalyst is 0.01 to 3.0 equivalent, preferably 0.01 to 1.5equivalents.

Examples of the halogenating agent include halogens such as bromine andchlorine; N-halosuccinimides such as N-bromosuccinimide andN-chlorosuccinimide; pyridine salts such as pyridinium perbromide;sulfuryl chloride, 1,3-dibromo-5,5-dimethylhydantoin, and the like.

Examples of the solvent include halogenated hydrocarbons such as1,2-dichloroethane, carbon tetrachloride, chlorobenzene, fluorobenzenand dichlorobenzene; benzene; carboxylic acids such as formic acid andacetic acid; water; and mixtures thereof. The amount of the solvent tobe used is in a ratio of 0.1 to 20 liters, preferably 0.1 to 5 liters ofthe solvent to 1 mol of the compound represented by the general formula[9].

Examples of the catalyst include benzoyl peroxide, a hydrogen peroxidesolution, α,α′-azobisisobutyronitrile, and mixtures thereof.

Examples of the base include alkali metal hydroxides such as sodiumhydroxide and potassium hydroxide; alkali metal carbonates such assodium carbonate and potassium carbonate; alkali metal bicarbonates suchas sodium hydrogen carbonate and potassium hydrogen carbonate; and thelike.

wherein R¹, R², R⁴, R⁷, R⁸, and X represent the same meanings asmentioned above.(Step 5)

The compound represented by the general formula [12] can be produced byreacting the compound represented by the general formula [10] with thecompound represented by the general formula [11] (thiourea) in asolvent.

With respect to the amounts of the reagents to be used, the amount ofthe a compound represented by the general formula [11] is desirably 1 to1.5 equivalents relative to 1 equivalent of the compound of the generalformula [10], but it can be optionally varied depending upon theconditions of the reaction.

Examples of the solvent include ethers such as dioxane andtetrahydrofuran; halogenated hydrocarbons such as dichloroethane, carbontetrachloride, chlorobenzene, and dichlorobenzene; aromatic hydrocarbonssuch as benzene, toluene, and xylene; amides such asN,N-dimethylacetamide, N,N-dimethylformamide, andN-methyl-2-pyrrolidinone; alcohols such as methanol, ethanol, and2-propanol; nitrites such as acetonitrile; ketones such as acetone andmethyl ethyl ketone; water; and mixtures thereof. The amount of thesolvent to be used is in a ratio of 0.1 to 20 liters, preferably 0.1 to5 liters of the solvent to 1 mol of the compound represented by thegeneral formula [10].

(Step 6)

The compound represented by the general formula [13] can be produced byhydrolyzing a compound represented by the general formula [12] in asolvent in the presence or absence of a base. In this step, the compoundmay be produced in the presence or absence of a reducing agent or underan inert gas stream. Moreover, the compound represented by the generalformula [13] may be used in the next reaction without isolation andpurification.

With respect to the amounts of the reagents to be used, the amount ofthe base is desirably 1 to 10 equivalents relative to 1 equivalent ofthe compound of the general formula [12], but it can be optionallyvaried depending upon the conditions of the reaction.

Examples of the solvent include ethers such as dioxane andtetrahydrofuran; halogenated hydrocarbons such as dichloroethane, carbontetrachloride, chlorobenzene, and dichlorobenzene; aromatic hydrocarbonssuch as benzene, toluene, and xylene; amides such asN,N-dimethylacetamide, N,N-dimethylformamide, andN-methyl-2-pyrrolidinone; sulfur compounds such as dimethyl sulfoxideand sulfolane; aromatic hydrocarbons such as benzene, toluene, andxylene; nitriles such as acetonitrile; alcohols such as methanol,ethanol, and 2-propanol; ketones such as acetone and methyl ethylketone; water; and mixtures thereof. The amount of the solvent to beused is in a ratio of 0.1 to 20 liters, preferably 0.1 to 5 liters ofthe solvent to 1 mol of the compound represented by the general formula[12].

Examples of the base include alkali metal carbonates such as sodiumcarbonate and potassium carbonate; alkali metal hydroxides such assodium hydroxide and potassium hydroxide; alkali metal bicarbonates suchas sodium hydrogen carbonate and potassium hydrogen carbonate; alkalimetal alcoholates such as sodium ethoxide and sodium methoxide; andorganic bases such as 1,8-diazabicyclo[5.4.0]-7-undecene.

Examples of the reducing agent include sodium borohydride and the like.

Examples of the inert gas include nitrogen, argon, and the like.

(Step 7)

The compound represented by the general formula [13] can be produced byreacting the compound represented by the general formula [10] with asulfide in a solvent in the presence or absence of a base. In this step,the compound may be produced in the presence or absence of a reducingagent or under an inert gas stream. Moreover, the compound representedby the general formula [13] may be used in the next reaction withoutisolation and purification.

With respect to the amounts of the reagents to be used, it is desirablethat the amount of the sulfide is 1 to 5 equivalents and the amount ofthe base is 1 to 10 equivalents, all relative to 1 equivalent of thecompound of the general formula [10], but these can be optionally varieddepending upon the conditions of the reaction.

Examples of the solvent include ethers such as dioxane andtetrahydrofuran; halogenated hydrocarbons such as dichloroethane, carbontetrachloride, chlorobenzene, and dichlorobenzene; aromatic hydrocarbonssuch as benzene, toluene, and xylene; amides such asN,N-dimethylacetamide, N,N-dimethylformamide, andN-methyl-2-pyrrolidinone; sulfur compounds such as dimethyl sulfoxideand sulfolane; aromatic hydrocarbons such as benzene, toluene, andxylene; nitrites such as acetonitrile; alcohols such as methanol,ethanol, and 2-propanol; ketones such as acetone and methyl ethylketone; water; and mixtures thereof. The amount of the solvent to beused is in a ratio of 0.1 to 20 liters, preferably 0.1 to 5 liters ofthe solvent to 1 mol of the compound represented by the general formula[10].

Examples of the sulfide include alkali metal sulfides such as sodiumsulfide and potassium sulfide; alkali metal hydrosulfides such as sodiumhydrosulfide and potassium hydrosulfide; hydrogen sulfide, ammoniumsulfide, sodium thioacetate, potassium thioacetate, and the like.

Examples of the base include alkali metal carbonates such as sodiumcarbonate and potassium carbonate; alkali metal hydroxides such assodium hydroxide and potassium hydroxide; alkali metal hydrides such aspotassium hydride and sodium hydride; alkali metal alcoholates such assodium ethoxide and sodium methoxide; and organic bases such as1,8-diazabicyclo[5.4.0]-7-undecene.

As the reducing agent and the inert gas, those the same as in Step 6 ofProduction Process 5 may be mentioned.

wherein R¹ and R² represent the same meanings as mentioned above.(Step 8)

The compound represented by the general formula [15] can be produced byreacting the compound of the general formula [14] withN,N-dimethylformamide in a solvent or in the absence of a solvent in thepresence of phosphoryl chloride, phosgene, or thionyl chloride inaccordance with the Vilsmeier method described in Org. Synth., Vol. IV,831 (1963), or by reacting the compound of the general formula [14] witha dihalogenomethyl ether in a solvent in the presence of a Lewis acid,followed by hydrolysis, in accordance with the method described in Chem.Ber., 93, 88 (1960).

This reaction is conducted ordinarily at −40 to 150° C. for 10 minutesto 24 hours.

With respect to the amounts of reagents to be used in the reaction, itis desired that the amount of phosphoryl chloride, phosgene, thionylchloride, N,N-dimethylformamide, Lewis acid, or dihalogenomethyl etheris 1 to 1.5 equivalents, relative to 1 equivalent of the compound of thegeneral formula [14], but the amount can be optionally varied dependingupon the conditions of the reaction.

Examples of the Lewis acid include titanium tetrachloride, tintetrachloride, zinc chloride, aluminum chloride, zinc bromide, and thelike.

Examples of the dihalogenomethyl ether include dichloromethyl methylether and the like.

Examples of the solvent include halogenated hydrocarbons such asdichloroethane, carbon tetrachloride, and chloroform; aliphatichydrocarbons such as hexane and heptane; ethers such as dioxane andtetrahydrofuran; carboxylic acids such as acetic acid; amides such asN,N-dimethylformamide; carbon disulfide; and mixtures thereof. Theamount of the solvent to be used is in a ratio of 0.1 to 20 liters,preferably 0.2 to 5 liters of the solvent to 1 mol of the compoundrepresented by the general formula [14].

wherein R¹, R², R⁴, and L¹ represent the same meanings as mentionedabove.(Step 9)

The compound represented by the general formula [17] can be produced byreacting the compound represented by the general formula [16] with thecompound represented by the general formula [5] in a solvent or in theabsence of a solvent (preferably in a suitable solvent) in the presenceor absence of a catalyst in the presence of a base.

With respect to the reaction temperature, all the reactions are carriedout at any temperature of 0° C. to a reflux temperature of the reactionsystem, preferably in the temperature range of 0° C. to 100° C. and thereaction may be conducted for 0.5 hour to 24 hours, although the periodvaries depending on the compounds.

With respect to the amounts of the reagents to be used in the reaction,the amount of the compound represented by the general formula [5] is 1to 5 equivalents, preferably 1 to 3 equivalents, the amount of the baseis 1 to 20 equivalents, preferably 1 to 10 equivalents, and the amountof the catalyst is 0.01 to 2.0 equivalents, preferably 0.01 to 0.5equivalent, all relative to 1 equivalent of the compound represented bythe general formula [16].

As the solvent, the base, and the catalyst, those the same as in Step 2of Production Process 2 may be mentioned.

wherein R¹, R², R⁴, and X represent the same meanings as mentionedabove.(Step 10)

The compound represented by the general formula [19] can be produced byreacting the compound represented by the general formula [18] with ahydrogen halide and formaldehyde or paraformaldehyde in a solvent in thepresence or absence of a Lewis acid, in accordance with the methoddescribed in Org. Synth., Vol. III, 557 (1955) or J. Amer. Chem. Soc.,72, 2216 (1950), or by reacting the compound represented by the generalformula [18] with a halogenomethyl ether in a solvent or without solventin the presence of a Lewis acid, in accordance with the method describedin J. Amer. Chem. Soc., 97, 6155 (1975).

This reaction is conducted ordinarily at −40 to 150° C. for 10 minutesto 24 hours.

With respect to the amounts of the reagents used, it is desired that theamount of the hydrogen halide is 1 to 2 equivalents, the amount offormaldehyde or paraformaldehyde is 1 to 2 equivalents, the amount ofthe Lewis acid is 1 to 2 equivalents, and the amount of thehalogenomethyl ether is 1 to 2 equivalents, all relative to 1 equivalentof the compound of the general formula [18]. However, these amounts canbe optionally varied depending upon the conditions of the reaction.

Examples of the Lewis acid include titanium tetrachloride, zincchloride, aluminum chloride, zinc bromide, and the like.

Examples of the hydrogen halide include hydrogen chloride, hydrogenbromide, and hydrogen iodide.

Examples of the halogenomethyl ether include chloromethyl methyl ether,bromomethyl methyl ether, and the like.

Examples of the solvent include halogenated hydrocarbons such asdichloroethane, carbon tetrachloride, and chloroform; aliphatichydrocarbons such as hexane and heptane; ethers such as dioxane andtetrahydrofuran; carboxylic acids such as acetic acid; carbon disulfide;and mixtures thereof. The amount of the solvent to be used is in a ratioof 0.1 to 20 liters, preferably 0.1 to 5 liters of the solvent to 1 molof the compound represented by the general formula [18].

In this connection, the compound represented by the general formula [18]can be produced by converting the hydrogen atom of the correspondingcompound wherein R⁴ is a hydrogen atom into the R⁴ in accordance withProduction Process 2 or 3.

The following will explain the processes for producing the inventivecompounds specifically. Also, physical properties of the inventivecompounds produced in respective Examples or produced in accordance withrespective Examples are shown.

EXAMPLE 1 Production of1-tert-butyl-5-difluoromethoxy-3-trifluoromethyl-1H-pyrazole (InventiveCompound No. 021)

To a solution of 10.4 g (50.0 mmol) of1-tert-butyl-5-hydroxy-3-trifluoromethyl-1H-pyrazole in 50 ml ofN,N-dimethylformamide was added 7.6 g (55.0 mmol) of anhydrous potassiumcarbonate at room temperature. While the reaction solution was stirred,an excess amount of chlorodifluoromethane was introduced into thereaction solution at 80° C. After the confirmation of disappearance ofthe starting material, the introduction of chlorodifluoromethane wasstopped and the reaction solution was cooled to room temperature.Thereafter, the reaction solution was poured into water and extractedwith diisopropyl ether. The resulting organic layer was washed withwater and dried over anhydrous magnesium sulfate. The solvent wasremoved by evaporation under reduced pressure and the residue wasdistilled under reduced pressure to obtain 10.8 g (yield: 83.7%) of1-tert-butyl-5-difluoromethoxy-3-trifluoromethyl-1H-pyrazole as a yellowliquid.

¹H-NMR value (CDCl₃/TMS δ (ppm)): 6.53(1H, t, J=71.9 Hz), 6.14(1H, s),1.63(9H, s)

EXAMPLE 2 Production of1-tert-butyl-5-(2,2-difluoroethoxy)-3-trifluoromethyl-1H-pyrazole(Inventive Compound No. 022)

To a solution of 50.0 g (240.2 mmol) of1-tert-butyl-5-hydroxy-3-trifluoromethyl-1H-pyrazole in 1000 ml oftetrahydrofuran were added 75.6 g (288.2 mmol) of triphenylphosphine and23.7 g (288.8 mmol) of 2,2-difluoroethanol at room temperature, followedby stirring. Under ice-cooling, 58.3 g (288.3 mmol) of diisopropylazodicarboxylate was added into the reaction solution, followed by 5hours of stirring. After the completion of the reaction was confirmed,the reaction solution was poured into water and extracted with diethylether. The resulting organic layer was washed with water and dried overanhydrous magnesium sulfate. The solvent was removed by evaporationunder reduced pressure and the residue was distilled under reducedpressure to obtain 38.2 g (yield: 58.4%) of1-tert-butyl-5-(2,2-difluoroethoxy)-3-trifluoromethyl-1H--pyrazole.

Boiling point: 98 to 100° C./6 KPa (45 mmHg)

Refractive index (n^(D) ₂₀): 1.3921

¹H-NMR value (CDCl₃/TMS δ (ppm)): 6.10(1H, tt, J=3.8, 54.5 Hz), 5.84(1H,s), 4.25(2H, dt, J=3.8, 13.0 Hz), 1.60(9H, s)

EXAMPLE 3 Production of1-tert-butyl-4-chloromethyl-5-(2,2-difluoroethoxy)-3-trifluoromethyl-1H-pyrazole(Inventive Compound No. 141)

To a solution of 13.6 g (50.0 mmol) of1-tert-butyl-5-(2,2-difluoroethoxy)-3-trifluoromethyl-1H-pyrazole in 50ml of acetic acid were added 5.0 g (purity: 90%, 150.0 mmol) ofparaformaldehyde and 20.5 g (150.0 mmol) of zinc chloride at roomtemperature, followed by stirring. Furthermore, an excess amount ofhydrogen chloride was introduced into the reaction solution underice-cooling, followed by 1 hour of stirring. After the completion of thereaction was confirmed, the reaction solution was poured into water andextracted with diethyl ether. The resulting organic layer was washedwith water and dried over anhydrous magnesium sulfate. The solvent wasremoved by evaporation under reduced pressure and a gas chromatographicanalysis was conducted to confirm that1-tert-butyl-4-chloromethyl-5-(2,2-difluoroethoxy)-3-trifluoromethyl-1H-pyrazolewas formed in an amount of 50.1%.

EXAMPLE 4 Production of5-hydroxy-1-methyl-3-trifluoromethyl-1H-pyrazole-4-carbaldehyde(Inventive Compound No. 281)

Into 16.6 g (100.0 mmol) of5-hydroxy-1-methyl-3-trifluoromethyl-1H-pyrazole in 15.4 g ofN,N-dimethylformaldehyde was added 16.2 g (105.0 mmol) of phosphorusoxychloride at 0° C., followed by 1 hour of stirring at roomtemperature. Furthermore, the whole was stirred at 100° C. for 1 hour.After the completion of the reaction was confirmed, the reactionsolution was poured into water and the pH was made 10 or more with a 25%sodium hydroxide solution and then the aqueous layer was washed withethyl acetate. The pH of the resulting aqueous layer was made about 4with a saturated citric acid solution and then extracted with diethylether. The resulting organic layer was washed with water and saline,successively, and then dried over anhydrous magnesium sulfate. Thesolvent was removed by evaporation under reduced pressure and theresidue was purified by silica gel column chromatography to obtain 4.5 g(yield: 23.2%) of5-hydroxy-1-methyl-3-trifluoromethyl-1H-pyrazole-4-carbaldehyde.

EXAMPLE 5 Production of5-difluoromethoxy-1-methyl-3-trifluoromethyl-1H-pyrazole-4-carbaldehyde(Inventive Compound No. 026)

To 1.7 g (8.8 mmol) of 5-hydroxy-1-methyl-3-trifluoromethyl-1H-pyrazolein 20 ml of tetrahydrofuran were added 2.5 g (43.8 mmol) of powderypotassium hydroxide and 0.14 g (0.44 mmol) of tetrabutylammonium bromideat room temperature, followed by stirring. Furthermore,chlorodifluoromethane was introduced into the reaction solution untilthe reaction system was saturated therewith. Thereafter, the whole wasstirred at room temperature overnight. After the completion of thereaction was confirmed, the reaction solution was poured into water andextracted with diethyl ether. The resulting organic layer was washedwith water and saline, successively, and then dried over anhydrousmagnesium sulfate. The solvent was removed by evaporation under reducedpressure and a gas chromatographic analysis was conducted to confirmthat5-difluoromethoxy-1-methyl-3-trifluoromethyl-1H-pyrazole-4-carbaldehydewas formed in an amount of 8.8%.

EXAMPLE 6 Production of1,4-dimethyl-5-hydroxy-3-trifluoromethyl-1H-pyrazole (Inventive CompoundNo. 036)

To a solution of 20.9 g (454.2 mmol) of methylhydrazine in 500 ml ofethanol was added dropwise under stirring 90.0 g (454.2 mmol) of ethyl4,4,4-trifluoro-2-methyl-3-oxobutanoate under ice-cooling so that thetemperature did not exceed 10° C. After the completion of the dropwiseaddition, the whole was stirred at room temperature for 30 minutes.Then, 10 ml of concentrated hydrochloric acid was added into thereaction solution, followed by 2 days of stirring under refluxing. Afterthe completion of the reaction was confirmed, the solvent was removed byevaporation under reduced pressure. Water was added to the residue,followed by extraction with ethyl acetate. The resulting organic layerwas washed with water and saline, successively, and then dried overanhydrous magnesium sulfate. The solvent was removed by evaporationunder reduced pressure and the residue was washed with n-hexane toobtain 61.0 g (yield: 74.6%) of1,4-dimethyl-5-hydroxy-3-trifluoromethyl-1H-pyrazole as white crystals(melting point: 148 to 151° C.).

¹H-NMR value (CDCl₃/TMS δ (ppm)): 3.70(3H, d), 1.99(3H, d)

Melting point: 148 to 151° C.

EXAMPLE 7 Production of5-difluoromethoxy-1,4-dimethyl-3-trifluoromethyl-1H-pyrazole (InventiveCompound No. 076)

Into 78.6 g (436.4 mmol) of1,4-dimethyl-5-hydroxy-3-trifluoromethyl-1H-pyrazole in 500 ml of2-propanol was added 153.1 g (2728.6 mmol) of powdery potassiumhydroxide at room temperature, followed by stirring. Furthermore, anexcess amount of chlorodifluoromethane was introduced into the reactionsolution under stirring. Thereafter, the reaction temperature once roseto 70° C. by exothermic heat and then returned to room temperature after2 hours. After the completion of the reaction was confirmed, thereaction solution was poured into water and extracted with ethylacetate. The resulting organic layer was washed with water and saline,successively, and then dried over anhydrous magnesium sulfate. Thesolvent was removed by evaporation under reduced pressure and theresidue was distilled to obtain 88.9 g (yield: 88.5%) of5-difluoromethoxy-1,4-dimethyl-3-trifluoromethyl-1H-pyrazole as acolorless transparent liquid.

¹H-NMR value (CDCl₃/TMS δ (ppm)): 6.52(1H, t, J=71.5 Hz), 3.78(3H, s),2.07(3H, s)

Boiling point: 98 to 100° C./6 KPa (45 mmHg)

Refractive index (n^(D) ₂₀): 1.3921

EXAMPLE 8 Production of4-bromomethyl-5-difluoromethoxy-1-methyl-3-trifluoromethyl-1H-pyrazole(Inventive Compound No. 151)

To a solution of 11.5 g (50.0 mmol) of5-difluoromethoxy-1,4-dimethyl-3-trifluoromethyl-1H-pyrazole in 50 ml ofcarbon tetrachloride were added 9.8 g (55.0 mmol) of N-bromosuccinimideand 0.41 (2.5 mmol) of α,α′-azobisisobutyronitrile, followed by heatingand refluxing under stirring. The reaction solution was externallyirradiated with a light for 1 hour. After the completion of the reactionwas confirmed, the reaction solution was poured into water and extractedwith chloroform. The resulting organic layer was washed with water andsaline, successively, and then dried over anhydrous magnesium sulfate.The solvent was removed by evaporation under reduced pressure to obtain17.8 g (purity: 72.0%, yield: 82.7%) of4-bromomethyl-5-difluoromethoxy-1-methyl-3-trifluoromethyl-1H-pyrazole.

¹H-NMR value (CDCl₃/TMS δ (ppm)): 6.73(1H, t, J=71.5 Hz), 4.39(2H, s),3.82(3H, d)

Refractive index (n^(D) ₂₀): 1.4401

EXAMPLE 9 Production of4-bromomethyl-5-difluoromethoxy-1-methyl-3-trifluoromethyl-1H-pyrazole(Inventive Compound No. 151)

To a solution of 0.50 g (2.17 mmol) of5-difluoromethoxy-1,4-dimethyl-3-trifluoromethyl-1H-pyrazole in 5 ml ofcarbon tetrachloride were added 0.90 g (5.64 mmol) of bromine and aminute amount of benzoyl peroxide, followed by heating and refluxingunder stirring. The reaction solution was externally irradiated with alight for 2 hours and 30 minutes. After the completion of the reaction,a gas chromatographic analysis was conducted to confirm that4-bromomethyl-5-difluoromethoxy-1-methyl-3-trifluoromethyl-1H-pyrazolewas formed in an amount of 80.2%.

EXAMPLE 10 Production of2-(5-difluoromethoxy-1-methyl-3-trifluoromethyl-1H-pyrazole-4-ylmethyl)-isothioureahydrobromide (Inventive Compound No. 197)

To a solution of 19.1 g (purity: 75.0%, 46.3 mmol) of4-bromomethyl-5-difluoromethoxy-1-methyl-3-trifluoromethyl-1H-pyrazolein 30 ml of ethanol was added 3.5 g (46.3 mmol) of thiourea, followed by1 hour of heating and refluxing under stirring. The solvent was removedby evaporation under reduced pressure and the residue was washed with amixed solvent of ethyl acetate and n-hexane to obtain 13.8 g (yield:77.5%) of2-(5-difluoromethoxy-1-methyl-3-trifluoromethyl-1H-pyrazole-4-ylmethyl)-isothioureahydrobromide as white crystals (melting point: 130 to 131° C.).

¹H-NMR value (CDCl₃+DMSO-d6/TMS δ (ppm)): 9.21(2H, br), 9.12(2H, br),6.92(1H, t, J=71.2 Hz), 4.40(2H, s), 3.83(3H, s)

EXAMPLE 11 Production of(5-difluoromethoxy-1-methyl-3-trifluoromethyl-1H-pyrazole-4-yl)-methanethiol(Inventive Compound No. 216)

To a solution of 1.00 g (2.60 mmol) of2-(5-difluoromethoxy-1-methyl-3-trifluoromethyl-1H-pyrazole-4-ylmethyl)-isothioureahydrobromide in 2 ml of N,N-dimethylformamide were added 0.43 g (3.12mmol) of anhydrous potassium carbonate and 1 ml of water, followed by 1hour of stirring at room temperature. After the completion of thereaction was confirmed, the reaction solution was poured into water andextracted with diethyl ether. The resulting organic layer was washedwith water and then dried over anhydrous magnesium sulfate. The solventwas removed by evaporation under reduced pressure to obtain 0.66 g(purity: 84.9%, yield: 82.4%) of(5-difluoromethoxy-1-methyl-3-trifluoromethyl-1H-pyrazole-4-yl)-methanethiol.

¹H-NMR value (CDCl₃/TMS δ (ppm)): 6.72(1H, t, J=71.7 Hz), 3.81 (3H, s),3.63(2H, s), 3.20(1H, br)

EXAMPLE 12 Production of(5-difluoromethoxy-1-methyl-3-trifluoromethyl-1H-pyrazole-4-yl)-methanethiol(Inventive Compound No. 216)

To a solution of 1.55 g (5.00 mmol) of4-bromomethyl-5-difluoromethoxy-1-methyl-3-trifluoromethyl-1H-pyrazolein 10 ml of ethanol was added 0.48 g (purity: 70.0%, 6.00 mmol) ofsodium hydrosulfide n-hydrate, followed by 1 hour of stirring at roomtemperature. After the completion of the reaction, a gas chromatographicanalysis was conducted to confirm that(5-difluoromethoxy-1-methyl-3-trifluoromethyl-1H-pyrazole-4-yl)-methanethiolwas formed in an amount of 40.0%.

EXAMPLE 13 Production of4-chloromethyl-5-difluoromethoxy-1-methyl-3-trifluoromethyl-1H-pyrazole(Inventive Compound No. 123)

To a solution of 11.5 g (50.0 mmol) of5-difluoromethoxy-1,4-dimethyl-3-trifluoromethyl-1H-pyrazole in 50 ml ofcarbon tetrachloride were added 10.1 g (75.0 mmol) of sulfuryl chlorideand 0.8 (5.0 mmol) of α,α′-azobisisobutyronitrile, followed by heatingand refluxing under stirring. The reaction solution was externallyirradiated with a light for 11 hours. After the completion of thereaction was confirmed, the reaction solution was poured into water andextracted with chloroform. The resulting organic layer was washed withwater and saline, successively, and then dried over anhydrous magnesiumsulfate. The solvent was removed by evaporation under reduced pressureand the residue was purified by silica gel column chromatography toobtain 4.8 g (purity: 83.4%, yield: 30.3%) of4-chloromethyl-5-difluoromethoxy-1-methyl-3-trifluoromethyl-1H-pyrazoleas a colorless transparent liquid.

¹H-NMR value (CDCl₃/TMS δ (ppm)): 6.69(1H, t, J=71.5 Hz), 4.51(2H, s),3.82(3H, s)

Refractive index (n^(D) ₂₀): 1.4157

EXAMPLE 14 Production of4-chloromethyl-5-difluoromethoxy-1-methyl-3-trifluoromethyl-1H-pyrazole(Inventive Compound No. 123)

To a solution of 1.00 g (4.35 mmol) of5-difluoromethoxy-1,4-dimethyl-3-trifluoromethyl-1H-pyrazole in 10 ml ofcarbon tetrachloride was added 0.55 g (6.52 mmol) of sodium hydrogencarbonate, followed by heating and refluxing under stirring. Thereaction solution was externally irradiated with a light and chlorinegas was introduced in a suitable amount while the amount of the aimedcompound formed was confirmed by gas chromatography. After thecompletion of the reaction, a gas chromatographic analysis was conductedto confirm that4-chloromethyl-5-difluoromethoxy-1-methyl-3-trifluoromethyl-1H-pyrazolewas formed in an amount of 61.7%.

EXAMPLE 15 Production of2-(5-difluoromethoxy-1-methyl-3-trifluoromethyl-1H-pyrazole-4-ylmethyl)-isothioureahydrochloride (Inventive Compound No. 178)

To a solution of 3.7 g (purity: 83.4%, 11.7 mmol) of4-chloromethyl-5-difluoromethoxy-1-methyl-3-trifluoromethyl-1H-pyrazolein 20 ml of ethanol was added 0.8 g (11.1 mmol) of thiourea, followed bystirring at room temperature overnight and further heating and stirringat 50° C. for 1 hour. The solvent was removed by evaporation underreduced pressure and the residue was washed with n-hexane to obtain 3.8g (yield: 96.4%) of2-(5-difluoromethoxy-1-methyl-3-trifluoromethyl-1H-pyrazole-4-ylmethyl)-isothioureahydrochloride as white crystals (melting point: 117 to 119° C.)

EXAMPLE 16 Production of1-ethyl-5-hydroxy-4-methyl-3-trifluoromethyl-1H-pyrazole (InventiveCompound No. 037)

To a solution of 1.2 g (20.0 mmol) of ethylhydrazine in 20 ml of ethanolwas added dropwise under stirring 4.4 g (20.0 mmol) of ethyl4,4,4-trifluoro-2-methyl-3-oxobutanoate under ice-cooling so that thetemperature in the reaction system did not exceed 10° C. After thedropwise addition, the whole was stirred at room temperature for 30minutes. Then, 1 ml of concentrated hydrochloric acid was added into thereaction solution, followed by 2 days of stirring under refluxing. Afterthe completion of the reaction was confirmed, the solvent was removed byevaporation under reduced pressure. Water was added to the residue,followed by extraction with ethyl acetate. The resulting organic layerwas washed with water and saline, successively, and then dried overanhydrous magnesium sulfate. The solvent was removed by evaporationunder reduced pressure and the residue was washed with n-hexane toobtain 2.8 g (yield: 71.8%) of1-ethyl-5-hydroxy-4-methyl-3-trifluoromethyl-1H-pyrazole as whitecrystals (melting point: 150 to 152° C.).

¹H-NMR value (CDCl₃/TMS δ (ppm)): 6.78(1H, br), 4.06(2H, q), 1.98(3H,d), 1.37(3H, t)

EXAMPLE 17 Production of5-hydroxy-4-methyl-1-iso-propyl-3-trifluoromethyl-1H-pyrazole (InventiveCompound No. 038)

To a solution of 7.4 g (100.0 mmol) of isopropylhydrazine in 100 ml ofethanol was added dropwise under stirring 23.3 g (purity: 85.0%, 100.0mmol) of ethyl 4,4,4-trifluoro-2-methyl-3-oxobutanoate under ice-coolingso that the temperature in the reaction system did not exceed 10° C.After the dropwise addition, the whole was stirred at room temperaturefor 30 minutes. Then, 1 ml of concentrated hydrochloric acid was addedinto the reaction solution, followed by 2 days of stirring underrefluxing. After the completion of the reaction was confirmed, thesolvent was removed by evaporation under reduced pressure. Water wasadded to the residue, followed by extraction with ethyl acetate. Theresulting organic layer was washed with water and saline, successively,and then dried over anhydrous magnesium sulfate. The solvent was removedby evaporation under reduced pressure and the residue was washed withn-hexane to obtain 18.1 g (yield: 87.0%) of5-hydroxy-4-methyl-1-iso-propyl-3-trifluoromethyl-1H-pyrazole as whitecrystals (melting point: 150 to 153° C.).

¹H-NMR value (CDCl₃/TMS δ (ppm)): 4.58(1H, m), 1.98(3H, d), 1.44(6H, d)

EXAMPLE 18 Production of5-difluoromethoxy-4-methyl-1-iso-propyl-3-trifluoromethyl-1h-pyrazole(Inventive Compound No. 084)

Into 17.1 g (82.1 mmol) of5-hydroxy-4-methyl-1-iso-propyl-3-trifluoromethyl-1H-pyrazole in 100 mlof 2-propanol was added 23.0 g (410.7 mmol) of powdery potassiumhydroxide at room temperature, followed stirring. Furthermore, stirringwas continued while an excess amount of chlorodifluoromethane wasintroduced into the reaction solution. Thereafter, the reactiontemperature once rose to 70° C. by exothermic heat and then returned toroom temperature after 2 hours. After the completion of the reaction wasconfirmed, the reaction solution was poured into water and extractedwith ethyl acetate. The resulting organic layer was washed with waterand saline, successively, and then dried over anhydrous magnesiumsulfate. The solvent was removed by evaporation under reduced pressureand the residue was distilled to obtain 15.9 g (yield: 75.0%) of5-difluoromethoxy-4-methyl-1-iso-propyl-3-trifluoromethyl-1H-pyrazole asa colorless transparent liquid.

¹H-NMR value (CDCl₃/TMS δ (ppm)): 6.52(1H, t, J=71.5 Hz), 4.58(1H, m),1.98(3H, d), 1.44(6H, d)

Boiling point: 84 to 86° C./3.33 KPa (25 mmHg)

Refractive index (n^(D) ₂₀): 1.3974

EXAMPLE 19 Production of4-bromomethyl-5-difluoromethoxy-1-iso-propyl-3-trifluoromethyl-1H-pyrazole(Inventive Compound No. 158)

To a solution of 10.3 g (40.0 mmol) of5-difluoromethoxy-4-methyl-1-iso-propyl-3-trifluoromethyl-1H-pyrazole in40 ml of carbon tetrachloride were added 7.8 g (44.0 mmol) ofN-bromosuccinimide and 0.3 (2.0 mmol) of α,α′-azobisisobutyronitrile,followed by heating and refluxing under stirring. The reaction solutionwas externally irradiated with a light for 1 hour. After the completionof the reaction was confirmed, the reaction solution was poured intowater and extracted with chloroform. The resulting organic layer waswashed with water and saline, successively, and then dried overanhydrous magnesium sulfate. The solvent was removed by evaporationunder reduced pressure and the residue was purified by silica gel columnchromatography to obtain 5.5 g (yield: 40.7%) of4-bromomethyl-5-difluoromethoxy-1-iso-propyl-3-trifluoromethyl-1H-pyrazole.

¹H-NMR value (CDCl₃/TMS δ (ppm)): 6.72(1H, t, J=71.9 Hz), 4.62(1H, m),4.40(2H, s), 1.47(6H, d, J=6.8 Hz)

Refractive index (n^(D) ₂₀): 1.4383

EXAMPLE 20 Production of1,4-dimethyl-5-(2,2,2-trifluoroethoxy)-3-trifluoromethyl-1H-pyrazole(Inventive Compound No. 079)

To a solution of 4.4 g (24.4 mmol) of1,4-dimethyl-5-hydroxy-3-trifluoromethyl-1H-pyrazole in 50 ml ofN,N-dimethylformamide were added 5.1 g (36.6 mmol) of anhydrouspotassium carbonate and 6.3 (26.8 mmol) of 2,2,2-trifluoroethyltrifluoromethanesulfonate, followed by 3 hours of stirring at roomtemperature. After the completion of the reaction was confirmed, thereaction solution was poured into water and extracted with ethylacetate. The resulting organic layer was washed with water and saline,successively, and then dried over anhydrous magnesium sulfate. Thesolvent was removed by evaporation under reduced pressure to obtain 6.1g (yield: 95.3%) of1,4-dimethyl-5-(2,2,2-trifluoroethoxy)-3-trifluoromethyl-1H-pyrazole asa pale yellow liquid.

¹H-NMR value (CDCl₃/TMS δ (ppm)): 4.41(2H, q), 3.74(3H, d), 2.08(3H, d)

Refractive index (n^(D) ₂₀): 1.3872

EXAMPLE 21 Production of5-(2,2-difluoroethoxy)-1,4-dimethyl-3-trifluoromethyl-1H-pyrazole(Inventive Compound No. 078)

To a solution of 9.0 g (50.0 mmol) of1,4-dimethyl-5-hydroxy-3-trifluoromethyl-1H-pyrazole in 50 ml oftetrahydrofuran were added 14.4 g (55.0 mmol) of triphenylphosphine and4.5 g (55.0 mmol) of 2,2-difluoroethanol at room temperature, followedby stirring. Furthermore, 12.3 g (60.0 mmol) of diisopropylazodicarboxylate was added thereto under ice-cooling, followed bystirring at room temperature overnight. After the completion of thereaction was confirmed, the reaction solution was poured into water andextracted with ethyl acetate. The resulting organic layer was washedwith water and saline, successively, and then dried over anhydrousmagnesium sulfate. The solvent was removed by evaporation under reducedpressure and the residue was purified by silica gel columnchromatography to obtain 6.8 g (yield: 55.7%) of1,4-dimethyl-5-(2,2-difluoroethoxy)-3-trifluoromethyl-1H-pyrazole as apale yellow liquid.

¹H-NMR value (CDCl₃/TMS δ (ppm)): 6.05(1H, tt, J=3.8, 54.3 Hz), 4.27(2H,dt, J=3.8, 13.5 Hz), 3.73(3H, s), 2.08(3H, d)

Refractive index (n^(D) ₂₀): 1.4070

EXAMPLE 22 5-Hydroxy-4-methyl-1-n-propyl-3-trifluoromethyl-1H-pyrazole(Inventive Compound No. 039)

¹H-NMR value (CDCl₃/TMS δ (ppm)): 8.75(1H, br), 3.94(2H, t), 1.96(3H,d), 1.77(2H, m), 0.88(3H, t)

Melting point: 133 to 134° C.

EXAMPLE 23 1-n-Butyl-5-hydroxy-4-methyl-3-trifluoromethyl-1H-pyrazole(Inventive Compound No. 040)

¹H-NMR value (CDCl₃/TMS δ (ppm)): 7.73(1H, br), 3.98(2H, t), 1.97(3H,d), 1.74(2H, m), 1.29(2H, m), 0.91(3H, t)

Melting point: 132 to 133° C.

EXAMPLE 24 1-tert-Butyl-5-hydroxy-4-methyl-3-trifluoromethyl-1H-pyrazole(Inventive Compound No. 043)

¹H-NMR value (CDCl₃/TMS δ (ppm)): 5.45(1H, br), 1.97(3H, d), 1.60(9H, s)

Melting point: 159 to 160° C.

EXAMPLE 255-Difluoromethoxy-4-methyl-1-ethyl-3-trifluoromethyl-1H-pyrazole(Inventive Compound No. 080)

¹H-NMR value (CDCl₃/TMS δ (ppm)): 6.49(1H, t, J=71.9 Hz), 4.10(2H, q),2.07(3H, d), 1.42(3H, t)

Boiling point: 88 to 91° C./3.73 KPa (28 mmHg)

Refractive index (n^(D) ₂₀): 1.3971

EXAMPLE 261-Ethyl-4-methyl-5-(2,2,2-trifluoroethoxy)-3-trifluoromethyl-1H-pyrazole(Inventive Compound No. 083)

¹H-NMR value (CDCl₃/TMS δ (ppm)): 4.42 (2H, q), 4.07 (2H, q), 2.09(3H,d), 1.41(3H, t)

EXAMPLE 274-Methyl-1-iso-propyl-5-(2,2,2-trifluoroethoxy)-3-trifluoromethyl-1H-pyrazole(Inventive Compound No. 087)

¹H-NMR value (CDCl₃/TMS δ (ppm)): 4.55(1H, m), 4.41(2H, q), 2.08(3H, d),1.45(6H, d)

EXAMPLE 284-Methyl-1-n-propyl-5-(2,2,2-trifluoroethoxy)-3-trifluoromethyl-1H-pyrazole(Inventive Compound No. 090)

¹H-NMR value (CDCl₃/TMS δ (ppm)): 4.41(2H, q), 3.97(2H, t), 2.09(3H, d),1.84(2H, m), 0.91(3H, t)

EXAMPLE 291-n-Butyl-4-methyl-5-(2,2,2-trifluoroethoxy)-3-trifluoromethyl-1H-pyrazole(Inventive Compound No. 093)

¹H-NMR value (CDCl₃/TMS δ (ppm)): 4.41(2H, q), 4.00(2H, t), 2.09(3H, d),1.80(2H, m), 1.30(2H, m), 0.93(3H, t)

EXAMPLE 301-tert-Butyl-4-methyl-5-(2,2,2-trifluoroethoxy)-3-trifluoromethyl-1H-pyrazole(Inventive Compound No. 102)

¹H-NMR value (CDCl₃/TMS δ (ppm)): 4.43(2H, q), 2.09(3H, d), 1.59(9H, s)

EXAMPLE 314-Ethyl-1-methyl-5-difluoromethoxy-3-trifluoromethyl-1H-pyrazole(Inventive Compound No. 105)

¹H-NMR value (CDCl₃/TMS δ (ppm) ): 6.50 (1H, t, J=71.7 Hz), 3.78(3H, s),2.51(2H, q), 1.15(3H, t)

Refractive index (n^(D) ₂₀): 1.4021

EXAMPLE 324-Bromomethyl-1-methyl-5-(2,2-difluoroethoxy)-3-trifluoromethyl-1H-pyrazole(Inventive Compound No. 153)

¹H-NMR value (CDCl₃/TMS δ (ppm) ): 6.11(1H, tt, J=3.5, 54.2 Hz),4.52(2H, dt, J=3.5, 13.5 Hz), 4.43(2H, s), 3.76(3H, s)

Refractive index (n^(D) ₂₀): 1.4490

EXAMPLE 334-Bromomethyl-1-methyl-5-(2,2,2-trifluoroethoxy)-3-trifluoromethyl-1H-pyrazole(Inventive Compound No. 154)

¹H-NMR value (CDCl₃/TMS δ (ppm)): 4.68(2H, q), 4.41(2H, s), 3.77(3H, s)

Refractive index (n^(D) ₂₀): 1.3872

EXAMPLE 344-Bromomethyl-5-difluoromethoxy-1-ethyl-3-trifluoromethyl-1H-pyrazole(Inventive Compound No. 155)

¹H-NMR value (CDCl₃/TMS δ (ppm) ): 6.73 (1H, t, J=71.7 Hz), 4.40(2H, s),4.13(2H, q), 1.46(3H, t)

EXAMPLE 354-Bromomethyl-1-tert-butyl-5-(2,2-difluoroethoxy)-3-trifluoromethyl-1H-pyrazole(Inventive Compound No. 168)

¹H-NMR value (CDCl₃/TMS δ (ppm)): 6.15 (1H, tt, J=3.7, 54.1 Hz),4.56(2H, dt, J=3.7, 13.4 Hz), 4.45(2H, s), 1.60(9H, s)

EXAMPLE 362-(5-(2,2-difluoroethoxy)-1-methyl-3-trifluoromethyl-1H-pyrazole-4-ylmethyl)-isothioureahydrobromide (Inventive Compound No. 199)

1H-NMR value (CD₃OD/TMS δ (ppm)): 6.26(1H, tt, J=3.4, 53.9 Hz), 4.51(2H,dt, J=3.2, 14.1 Hz), 4.41(2H, s), 3.78(3H, s)

EXAMPLE 372-(5-(2,2,2-trifluoroethoxy)-1-methyl-3-trifluoromethyl-1H-pyrazole-4-ylmethyl)-isothioureahydrobromide (Inventive Compound No. 200)

Melting point: 128 to 131° C.

EXAMPLE 382-(5-difluoromethoxy-1-ethyl-3-trifluoromethyl-1H-pyrazole-4-ylmethyl)-isothioureahydrobromide (Inventive Compound No. 201)

Melting point: 139 to 141° C.

EXAMPLE 392-(5-difluoromethoxy-1-iso-propyl-3-trifluoromethyl-1H-pyrazole-4-ylmethyl)-isothioureahydrobromide (Inventive Compound No. 204)

Melting point: 146 to 148° C.

EXAMPLE 40(5-Difluoromethoxy-1-iso-propyl-3-trifluoromethyl-1H-pyrazole-4-yl)-methanethiol(Inventive Compound No. 223)

¹H-NMR value (CDCl₃/TMS δ (ppm)): 6.72(1H, t, J=72.2 Hz), 4.60(1H, m),3.62(2H, s), 1.46(6H, d)

In addition to the above compounds, with respect to the compounds shownby Compound Nos. in the following table, values of physical propertiesand data of instrumental analysis were confirmed. TABLE 12 Compound No.Value of physical property or NMR data 037 melting point: 150 to 152° C.038 melting point: 150 to 153° C. 151 ¹H-NMR value (CDCl₃/TMS δ (ppm)):6.73(1H, t, J=71.5Hz), 4.39(2H, s), 3.82(3H, d) Refractive index (n^(D)₂₀): 1.4401 178 melting point: 117 to 119° C. 197 melting point: 130 to131° C.

The following will explain the production of isoxazoline derivatives(described in Japanese Patent Laid-Open No. 308857/2002) using theinventive compounds represented by the general formula [I] asintermediates, and herbicidal action of the isoxazoline derivatives.

First, there will be explained the production of the isoxazolinederivatives (described in Japanese Patent Laid-Open No. 308857/2002)using the inventive compounds represented by the general formula [I].

wherein R¹, R², R⁴, R⁷, R⁸, and X represent the same meanings asmentioned above, R⁹ and R¹⁰ are the same or different from each otherand each represents a hydrogen atom, an alkyl group, a cycloalkyl group,or a cycloalkylalkyl group or R⁹ and R¹⁰ are combined together with thecarbon atom bonded thereto to form a C3 to C7 spiro ring, R¹¹ and R¹²are the same or different from each other and each represents a hydrogenatom, an alkyl group, or a cycloalkyl group or R¹¹ and R¹² are combinedtogether with the carbon atom bonded thereto to form a C3 to C7 Spiroring, and further R⁹, R¹⁰, R¹¹, and R¹² may form a 5 to 8-membered-ringtogether with the carbon atom bonded thereto. R¹³ represents a C1 to C4alkyl group, a phenyl group which may be substituted, or a benzyl groupwhich may be substituted and L represents a leaving group such as ahalogen atom, a C1 to C4 alkylsulfonyl group, a phenylsulfonyl groupwhich may be substituted, or a benzylsulfonyl group which may besubstituted.

The following will explain each step of the above processes forproducing isoxazoline derivatives.

(Step 11)

A sulfide derivative represented by the general formula [23] can beproduced by reacting a compound represented by the general formula [20]with sodium hydrosulfide hydrate represented by the general formula [21]in a solvent or in the absence of solvent (preferably in a suitablesolvent) in the presence of a base to produce a salt of a mercaptanrepresented by the general formula [22] in the reaction system and thenreacting the salt of the mercaptan [22], which was not isolated, withthe halogen derivative represented by the general formula [10] which isan inventive compound (optionally, the reaction is conducted under aninert gas atmosphere or a reducing agent can be added).

(Step 12)

A sulfoxide derivative represented by the general formula [25] can beproduced by reacting a sulfide derivative represented by the generalformula [23] with an oxidizing agent in a suitable solvent.

(Step 13)

A sulfone derivative represented by the general formula [26] can beproduced by reacting a sulfoxide derivative represented by the generalformula [25] with an oxidizing agent in a suitable solvent.

(Step 14)

The sulfone derivative represented by the general formula [26] can beproduced by reacting the sulfide derivative represented by the generalformula [23] with a suitable amount of an oxidizing agent in a suitablesolvent without isolating the sulfoxide derivative represented by thegeneral formula [25].

(Step 15)

The sulfide derivative represented by the general formula [23] can beproduced by reacting a compound represented by the general formula [24]with the mercaptan derivative represented by the general formula [13]which is an inventive compound in a solvent or in the absence of solvent(preferably in a suitable solvent) in the presence of a base(optionally, the reaction is conducted under an inert gas atmosphere ora reducing agent can be added). The mercaptan derivative represented bythe general formula [13] which is an inventive compound can be alsoproduced in the reaction system by the method described in Step 6 or 7of Production Process 5 and then employed.

The following will specifically explain the production of theisoxazoline derivatives (described in Japanese Patent Laid-Open No.308857/2002) using the inventive compounds represented by the generalformula [1] with reference to Reference Examples.

REFERENCE EXAMPLE 1 Production of3-(5-difluoromethoxy-1-methyl-3-trifluoromethyl-1H-pyrazole-4-ylmethylthio)-5,5-dimethyl-2-isoxazoline

1) To a solution of 6.7 g (35.0 mmol) of3-ethanesulfonyl-5,5-dimethyl-2-isoxazoline in 50 ml ofN,N-dimethylformamide was added 5.6 g (purity: 70%, 70.0 mmol) of sodiumhydrosulfide, followed by 1 hour of stirring at room temperature.Thereafter, 4.8 g (35.0 mmol) of potassium carbonate and 10.8 g (35.0mmol) of4-bromomethyl-5-difluoromethoxy-1-methyl-3-trifluoromethyl-1H-pyrazolewere added thereto, followed by stirring at room temperature overnight.After the completion of the reaction was confirmed, the reactionsolution was poured into water and extracted with ethyl acetate. Theresulting organic layer was washed with water and saline and then driedover anhydrous magnesium sulfate. The solvent was removed by evaporationunder reduced pressure and the residue was purified by silica gel columnchromatography to obtain 7.3 g (yield: 57.9%) of3-(5-difluoromethoxy-1-methyl-3-trifluoromethyl-1H-pyrazole-4-ylmethylthio)-5,5-dimethyl-2-isoxazolineas white crystals (melting point: 39 to 40° C.).

¹H-NMR value (CDCl₃/TMS δ (ppm)): 6.72(1H, t, J=72.0 Hz), 4.19(2H, s),3.81(3H, s), 2.78(2H, s), 1.42(6H, s)

2) To a solution of 1.93 g (5.00 mmol) of2-(5-difluoromethoxy-1-methyl-3-trifluoromethyl-1H-pyrazole-4-ylmethyl)-isothioureahydrobromide in 10 ml of ethanol were added 0.48 g (12.00 mmol) ofsodium hydroxide and 10 ml of -water, followed by 30 minutes of stirringat room temperature. Thereto was added 0.67 g (5.00 mmol) of3-chloro-5,5-dimethyl-2-isoxazoline at room temperature, followed byfurther 12 hours of stirring under refluxing. After the completion ofthe reaction was confirmed, the solvent was removed by evaporation underreduced pressure. The obtained residue was poured into water andextracted with ethyl acetate. The resulting organic layer was washedwith water and then dried over anhydrous magnesium sulfate. The solventwas removed by evaporation under reduced pressure and the residue waspurified by silica gel column chromatography to obtain 1.02 g (yield:56.7%) of3-(5-difluoromethoxy-1-methyl-3-trifluoromethyl-1H-pyrazole-4-ylmethylthio)-5,5-dimethyl-2-isoxazoline.

3) To a solution of 1.93 g (5.00 mmol) of2-(5-difluoromethoxy-1-methyl-3-trifluoromethyl-1H-pyrazole-4-ylmethyl)-isothioureahydrobromide in 10 ml of ethanol were added 0.83 g (6.00 mmol) ofanhydrous potassium carbonate and 5 ml of water, followed by 30 minutesof stirring at room temperature. Thereto were added a solution of 0.95 g(5.00 mmol) of 3-ethanesulfonyl-5,5-dimethyl-2-isoxazoline in 5 ml ofN,N-dimethylformamide and 0.83 g (6.00 mmol) of anhydrous potassiumcarbonate at room temperature, followed by further 3 hours of stirringat 50° C. After the completion of the reaction was confirmed, thesolvent was removed by evaporation under reduced pressure. The obtainedresidue was poured into water and extracted with ethyl acetate. Theresulting organic layer was washed with water and then dried overanhydrous magnesium sulfate. The solvent was removed by evaporationunder reduced pressure and the residue was purified by silica gel columnchromatography to obtain 1.55 g (yield: 86.1%) of3-(5-difluoromethoxy-1-methyl-3-trifluoromethyl-1H-pyrazole-4-ylmethylthio)-5,5-dimethyl-2-isoxazoline.

REFERENCE EXAMPLE 2 Production of3-(5-difluoromethoxy-1-methyl-3-trifluoromethyl-1H-pyrazole-4-ylmethanesulfinyl)-5,5-dimethyl-2-isoxazoline

To a solution of 6.2 g (17.3 mmol) of3-(5-difluoromethoxy-1-methyl-3-trifluoromethyl-1H-pyrazole-4-ylmethylthio)-5,5-dimethyl-2-isoxazolinein 40 ml of chloroform was added 3.4 g (purity: 70%, 13.8 mmol) ofm-chloroperbenzoic acid under ice-cooling, followed by 1 hour ofstirring. Thereafter, the whole was further stirred at room temperaturefor 3 hours. After the completion of the reaction was confirmed, thereaction solution was poured into water and extracted with chloroform.The resulting organic layer was washed with an aqueous sodium hydrogensulfite solution, an aqueous sodium hydrogen carbonate, water, andsaline, successively, and then dried over anhydrous magnesium sulfate.The solvent was removed by evaporation under reduced pressure and theresulting solid was washed with n-hexane to obtain 4.1 g (yield: 63.2%)of3-(5-difluoromethoxy-1-methyl-3-trifluoromethyl-1H-pyrazole-4-ylmethanesulfinyl)-5,5-dimethyl-2-isoxazolineas a white powder (melting point: 112 to 114° C.).

¹H-NMR value (CDCl₃/TMS δ (ppm)): 6.95(1H, q, J=69.5, 74.4 Hz), 4.16(2H,s), 3.85(3H, s), 3.11(2H, q, J=17.2 Hz), 1.52(6 H, d, J=5.5 Hz)

REFERENCE EXAMPLE 3 Production of3-(5-difluoromethoxy-1-methyl-3-trifluoromethyl-1H-pyrazole-4-yl-methanesulfonyl)-5,5-dimethyl-2-isoxazoline

To a solution of 7.3 g (20.3 mmol) of3-(5-difluoromethoxy-1-methyl-3-trifluoromethyl-1H-pyrazole-4-ylmethylthio)-5,5-dimethyl-2-isoxazolinein 50 ml of chloroform was added 12.5 g (purity: 70%, 50.8 mmol) ofm-chloroperbenzoic acid under ice-cooling, followed by 1 hour ofstirring. Thereafter, the whole was further stirred at room temperatureovernight. After the completion of the reaction was confirmed, thereaction solution was poured into water and extracted with chloroform.The resulting organic layer was washed with an aqueous sodium hydrogensulfite solution, an aqueous sodium hydrogen carbonate, water, andsaline, successively, and then dried over anhydrous magnesium sulfate.The solvent was removed by evaporation under reduced pressure and theresulting solid was washed with n-hexane to obtain 6.4 g (yield: 80.6%)of3-(5-difluoromethoxy-1-methyl-3-trifluoromethyl-1H-pyrazole-4-yl-methanesulfonyl)-5,5-dimethyl-2-isoxazolineas a white powder (melting point: 129 to 130° C.).

¹H-NMR value (CDCl₃/TMS δ (ppm)): 6.83(1H, t, J=71.9 Hz), 4.60(2H, s),3.88(3H, s), 3.11(2H, s), 1.52(6H, s)

REFERENCE EXAMPLE 43-(5-Difluoromethoxy-l-ethyl-3-trifluoromethyl-1H-pyrazole-4-yl-methanesulfonyl)-5,5-dimethyl-2-isoxazoline

Melting point: 98 to 100° C.

¹H-NMR value (CDCl₃/TMS δ (ppm)): 6.83(1H, t, J=72.0 Hz), 4.60(2H, s),4.19(2H, q), 3.11(2H, s), 1.51(6H, s), 1.49(3H, s)

REFERENCE EXAMPLE 53-(5-Difluoromethoxy-1-iso-propyl-3-trifluoromethyl-1H-pyrazole-4-yl-methanesulfonyl)-5,5-dimethyl-2-isoxazoline

Refractive index (n^(D) ₂₀): 1.4621

¹H-NMR value (CDCl₃/TMS δ (ppm)): 6.83(1H, t, J=72.1 Hz), 4.70(1H, m),4.60(2H, s), 3.10(2H, s), 1.52(6H, s), 1.49(6H, s)

REFERENCE EXAMPLE 63-(5-Difluoromethoxy-1-n-propyl-3-trifluoromethyl-1H-pyrazole-4-yl-methanesulfonyl)-5,5-dimethyl-2-isoxazoline

Refractive index (n^(D) ₂₀): 1.4629

¹H-NMR value (CDCl₃/TMS δ (ppm)): 6.82(1H, t, J=71.7 Hz), 4.60(2H, s),4.09(2H, t), 3.10(2H, s), 1.92(2H, m), 1.52(6H, s), 0.94(3H, t)

REFERENCE EXAMPLE 73-(1-iso-Butyl-5-difluoromethoxy-3-trifluoromethyl-1H-pyrazole-4-yl-methanesulfonyl)-5,5-dimethyl-2-isoxazoline

Refractive index (n^(D) ₂₀): 1.4601

¹H-NMR value (CDCl₃/TMS δ (ppm)): 6.81(1H, t, J=71.7 Hz), 4.60(2H, s),3.94(2H, d), 3.10(2H, s), 2.30(1H, m), 1.51(6H, m), 0.92(6H, d)

REFERENCE EXAMPLE 83-(5-Difluoromethoxy-1-methyl-3-trifluoromethyl-1H-pyrazole-4-yl-methanesulfonyl)-5-ethyl-5-methyl-2-isoxazoline

Melting point: 77 to 78° C.

¹H-NMR value (CDCl₃/TMS δ (ppm)): 6.83(1H, t, J=71.9 Hz), 4.60(2H, s),3.88(3H, s), 3.09(2H, ABq, J=17.4 Hz, Δν=46.7 Hz), 1.78(2H, q), 1.47(3H,s), 0.98(3H, t)

REFERENCE EXAMPLE 93-(5-Difluoromethoxy-1-methyl-3-trifluoromethyl-1H-pyrazole-4-yl-methanesulfonyl)-5-methyl-5-cyclopropyl-2-isoxazoline

Melting point: 96 to 98° C.

¹H-NMR value (CDCl₃/TMS δ (ppm)): 6.83(1H, t, J=71.9 Hz), 4.59(2H, s),3.88(3H, s), 3.13(2H, ABq, J=17.3 Hz, Δν=53.4 Hz), 1.48(3H, s), 1.14(1H,m), 0.36 to 0.58(4H, m)

REFERENCE EXAMPLE 107-(5-Difluoromethoxy-1-methyl-3-trifluoromethyl-1H-pyrazole-4-yl-methanesulfonyl)-5-oxa-6-azaspyro[3.4]-6-octene

Melting point: 149 to 151° C.

¹H-NMR value (CDCl₃/TMS δ (ppm)): 6.83(1H, t, J=71.9 Hz), 4.58(2H, s),3.87(3H, s), 3.40(2H, s), 2.62(2H, m), 2.27(2H, m), 1.91(1H, m),1.67(1H, m)

REFERENCE EXAMPLE 113-(5-Difluoromethoxy-1-methyl-3-trifluoromethyl-1H-pyrazole-4-yl-methanesulfonyl)-2-isoxazoline

Melting point: 115 to 117° C.

¹H-NMR value (CDCl₃/TMS δ (ppm)): 6.83(1H, t, J=71.7 Hz), 4.66(2H, t),4.61(2H, s), 3.88(3H, s), 3.37(2H, t)

REFERENCE EXAMPLE 126-(5-Difluoromethoxy-1-methyl-3-trifluoromethyl-1H-pyrazole-4-yl-methanesulfonyl)-4-oxa-5-azaspyro[2.4]-5-heptene

Melting point: 125 to 126° C.

¹H-NMR value (CDCl₃/TMS δ (ppm)): 6.83(1H, t, J=71.9 Hz), 4.61(2H, s),3.88(3H, s), 3.42(2H, s), 1.31(2H, t), 0.91(2H, t)

REFERENCE EXAMPLE 133-[1-(5-difluoromethoxy-1-methyl-3-trifluoromethyl-1H-pyrazole-4-yl)-ethanesulfonyl]-5,5-dimethyl-2-isoxazoline

Refractive index (n^(D) ₂₀): 1.4657

¹H-NMR value (CDCl₃/TMS δ (ppm)): 6.92(1H, m), 4.83(1H, q), 3.88(3H, s),3.07(2H, d), 1.83 (3H, d), 1.50(6H, d)

REFERENCE EXAMPLE 143-(5-Difluoromethoxy-1-methyl-3-trifluoromethyl-1H-pyrazole-4-yl-methanesulfonyl)-3a,4,5,6,7,7a-hexahydro-benzo[d]isoxazole

Melting point: 97 to 98° C.

¹H-NMR value (CDCl₃/TMS δ (ppm)): 6.84(1H, t, J=72.0 Hz), 4.69(1H, m),4.61(2H, s), 3.88(3H, s), 3.48(1H, m), 1.26 to 2.17(9H, m)

REFERENCE EXAMPLE 153-(5-Difluoromethoxy-1-methyl-3-trifluoromethyl-1H-pyrazole-4-yl-methanesulfonyl)-5-methyl-2-isoxazoline

Melting point: 106 to 107° C.

¹H-NMR value (CDCl₃/TMS δ (ppm)): 6.83(1H, t, J=71.9 Hz), 5.05(1H, m),4.60(2H, s), 3.88(3H, s), 3.44(1H, dd), 2.96(1H, dd), 1.48(3H, d)

REFERENCE EXAMPLE 163-(5-Difluoromethoxy-1-methyl-3-trifluoromethyl-1H-pyrazole-4-yl-methanesulfonyl)-5-iso-propyl-2-isoxazoline

Melting point: 85 to 86° C.

¹H-NMR value (CDCl₃/TMS δ (ppm)): 6.83(1H, t, J=71.7 Hz), 4.67(1H, m),4.59(2H, s), 3.88(3H, s), 3.30(1H, dd), 3.08(1H, dd), 1.97(1H, m),0.98(6H, dd)

REFERENCE EXAMPLE 173-(5-Difluoromethoxy-1-methyl-3-trifluoromethyl-1H-pyrazole-4-yl-methanesulfonyl)-4,5,5-trimethyl-2-isoxazoline

Refractive index (n^(D) ₂₀): 1.4646

1H-NMR value (CDCl₃/TMS δ (ppm)): 6.84(1H, t, J=71.9 Hz), 4.61(2H, q),3.88(3H, s), 3.36(1H, q), 1.44(3H, s), 1.38(3H, s), 1.30(3H, d)

REFERENCE EXAMPLE 183-(5-Difluoromethoxy-1-methyl-3-trifluoromethyl-1H-pyrazole-4-yl-methanesulfonyl)-4-methyl-2-isoxazoline

Refractive index (n^(D) ₂₀): 1.4673

¹H-NMR value (CDCl₃/TMS δ (ppm)): 6.83(1H, t, J=71.8 Hz), 4.71(1H, t),4.62(2H, q), 4.25(1H, t), 3.88(3H, s), 3.81(1H, m), 1.44(3H, d)

REFERENCE EXAMPLE 193-[1-(5-Difluoromethoxy-1-methyl-3-trifluoromethyl-1H-pyrazole-4-yl)-propane-1-sulfonyl]-5,5-dimethyl-2-isoxazoline

Refractive index (n^(D) ₂₀): 1.4669

¹H-NMR value (CDCl₃/TMS δ (ppm)): 6.91(1H, t, J=72.9 Hz), 4.60(1H, q),3.89(3H, s), 3.05(2H, d), 2.30(2H, m), 1.49(6H, d), 0.94(3H, t)

REFERENCE EXAMPLE 203-[5-(2,2,2-Trifluoroethoxy)-1-methyl-3-trifluoromethyl-1H-pyrazole-4-yl-methanesulfonyl]-5,5-dimethyl-2-isoxazoline

Melting point: 93 to 95° C.

¹H-NMR value (CDCl₃/TMS δ (ppm)): 4.68(2H, q), 4.59(2H, s), 3.84(3H, s),3.12(2H, s), 1.53(6H, s)

REFERENCE EXAMPLE 213-[5-(2,2-Difluoroethoxy)-1-methyl-3-trifluoromethyl-1H-pyrazole-4-yl-methanesulfonyl]-5,5-dimethyl-2-isoxazoline

Melting point: 89 to 91° C.

¹H-NMR value (CDCl₃/TMS δ (ppm)): 6.11(1H, tt, J=3.5, 54.4 Hz), 4.58(2H,s), 4.48(2H, dt, J=3.7, 15.3 Hz), 3.88(3H, s), 3.11(2H, s), 1.52(6H, s)

REFERENCE EXAMPLE 223-[1-tert-Butyl-5-(2,2-difluoroethoxy)-3-trifluoromethyl-1H-pyrazole-4-yl-methanesulfonyl]-5,5-dimethyl-2-isoxazoline

¹H-NMR value (CDCl₃/TMS δ (ppm)): 6.14(1H, tt, J=3.9, 54.4 Hz), 4.61(2H,s), 4.54(2H, dt, J=3.6, 13.4 Hz), 3.08(2H, s), 1.63(9H, s), 1.51(6H, s)

REFERENCE EXAMPLE 233-[5-(2,2-Difluoroethoxy)-1-iso-propyl-3-trifluoromethyl-1H-pyrazole-4-yl-methanesulfonyl]-5,5-dimethyl-2-isoxazoline

Melting point: 88 to 89° C.

¹H-NMR value (CDCl₃/TMS δ (ppm)): 6.11(1H, tt, J=3.4, 54.6 Hz), z), 4.58to 4.65(3H, m), 4.47(2H, dt, J=3.7, 13.4 Hz), 3.10 (2H, s), 1.52(6H, s),1.46(6H, d)

REFERENCE EXAMPLE 243-[1-Ethyl-5-(2,2-difluoroethoxy)-3-trifluoromethyl-1H-pyrazole-4-yl-methanesulfonyl]-5,5-dimethyl-2-isoxazoline

Refractive index (n^(D) ₂₀): 1.4687

¹H-NMR value (CDCl₃/TMS δ (ppm)): 6.11(1H, tt, J=3.7, 54.5 Hz), 4.58(2H,s), 4.48(2H, dt, J=3.7, 13.4 Hz), 4.16(2H, q), 3.10(2H, s), 1.52(6H, s),1.47(3H,t)

REFERENCE EXAMPLE 253-[5-(2,2-Difluoroethoxy)-1-n-propyl-3-trifluoromethyl-1H-pyrazole-4-yl-methanesulfonyl]-5,5-dimethyl-2-isoxazoline

Refractive index (n_(D) ₂₀): 1.4658

¹H-NMR value (CDCl₃/TMS δ (ppm)): 6.11(1H, tt, J=3.7, 54.3 Hz), 4.59(2H,s), 4.47(2H, dt, J=3.7, 13.5 Hz), 4.04(2H, t), 3.09(2H, t), 1.90(2H, m),1.52(6H, s), 0.94(3H, t)

REFERENCE EXAMPLE 263-[5-(2,2,2-Trifluoroethoxy)-1-iso-propyl-3-trifluoromethyl-1H-pyrazole-4-yl-methanesulfonyl]-5,5-dimethyl-2-isoxazoline

Melting point: 109 to 110° C.

¹H-NMR value (CDCl₃/TMS δ (ppm)): 4.55 to 4.70(5H, m), 3.11 (2H, s),1.52(6H, s), 1.49(6H, d)

REFERENCE EXAMPLE 273-[5-(2,2,2-Trifluoroethoxy)-1-n-propyl-3-trifluoromethyl-1H-pyrazole-4-yl-methanesulfonyl]-5,5-dimethyl-2-isoxazoline

Melting point: 49 to 51° C.

¹H-NMR value (CDCl₃/TMS δ (ppm)): 4.68(2H, q), 4.59(2H, s), 4.04(2H, t),3.11(2H, s), 1.88(2H, m), 1.52(6H, s), 0.94(3 H, t)

REFERENCE EXAMPLE 283-[1-n-Butyl-5-(2,2,2-trifluoroethoxy)-3-trifluoromethyl-1H-pyrazole-4-yl-methanesulfonyl]-5,5-dimethyl-2-isoxazoline

Refractive index (n^(D) ₂₀): 1.4533

¹H-NMR value (CDCl₃/TMS δ (ppm)): 4.67(2H, q), 4.59(2H, s) 4.07(2H, t),3.10(2H, s), 1.84(2H, m), 1.52(6H, s), 1.35(2 H, m), 0.95(3H, t)

REFERENCE EXAMPLE 293-[1-Ethyl-5-(2,2,2-trifluoroethoxy)-3-trifluoromethyl-1H-pyrazole-4-yl-methanesulfonyl]-5,5-dimethyl-2-isoxazoline

Melting point: 84 to 86° C.

¹H-NMR value (CDCl₃/TMS δ (ppm)): 4.68(2H, q), 4.59(2H, s), 4.14(2H, q),3.11(2H, s), 1.52(6H, s), 1.47(3H, t)

REFERENCE EXAMPLE 303-[1-tert-Butyl-5-(2,2,2-trifluoroethoxy)-3-trifluoromethyl-1H-pyrazole-4-yl-methanesulfonyl]-5,5-dimethyl-2-isoxazoline

Melting point: 91 to 92° C.

¹H-NMR value (CDCl₃/TMS δ (ppm)): 4.77(2H, q), 4.60(2H, s), 3.11(2H, s),1.63(9H, s), 1.52(6H, s)

The following will explain herbicidal action exhibited by the compoundrepresented by the general formula [26] (the isoxazoline derivativedescribed in Japanese Patent Laid-Open No. 308857/2002), which isproducible by using the pyrazole derivative represented by the generalformula [I] or salt thereof (inventive compound).

In using the compound represented by the general formula [26] (theisoxazoline derivative described in Japanese Patent Laid-Open No.308857/2002) as a herbicide, the compound may be used by itself but canbe also used as formulated in the form of a dust, a wettable powder, anemulsifiable concentrate, a flowable, a microgranule, a granule, or thelike by mixing with a carrier, a surfactant, a dispersing agent, anauxiliary agent, or the like which are commonly used for formulation.

Examples of the carrier to be used for the formulation include solidcarriers such as talc, bentonite, clay, kaolin, diatomaceous earth,white carbon, vermiculite, calcium carbonate, slaked lime, silica sand,ammonium sulfate, and urea; liquid carriers such as isopropyl alcohol,xylene, cyclohexane, and methylnaphthalene; and the like.

Examples of the surfactant and the dispersing agent include metal saltsof alkylbenzenesulfonic acids, metal salts ofdinaphthylmethanedisulfonic acid, salts of alcohol sulfate esters,alkylarylsulfonic acid salts, ligninsulfonic acid salts, polyoxyethyleneglycol ether, polyoxyethylene alkyl aryl ethers, monoalkylates ofpolyoxyethylene sorbitan, and the like. Examples of the auxiliary agentinclude carboxymethyl cellulose, polyethylene glycol, gum arabic, andthe like. At the use, it is diluted to an appropriate concentration andthen sprayed or applied directly.

The compound represented by the general formula [26] can be used byfoliar sparying, soil application, water surface application, or thelike. The amount of the active ingredient to be blended is suitablydetermined according to the necessity. When a powder or a granule isprepared, the amount may be suitably determined in the range of 0.01 to10% by weight, preferably 0.05 to 5% by weight. When an emulsifiableconcentrate or a wettable powder is prepared, the amount may be suitablydetermined in the range of 1 to 50% by weight, preferably 5 to 30% byweight. When a flowable is prepared, the amount may be suitablydetermined in the range of 1 to 40% by weight, preferably 5 to 30% byweight.

The amount of the compound represented by the general formula [26] as aherbicide to be applied varies depending upon the kind of the compoundused, the target weed, the tendency of weed emergence, the environmentalconditions, the form to be used, and the like. When the compound is usedper se as in the case of a powder or a granule, the amount is suitablydetermined in the range of 1 g to 50 kg, preferably 10 g to 10 kg per 1hectare in terms of the active ingredient. When the compound is used ina liquid form as in the case of an emulsifiable concentrate, a wettablepowder, or a flowable, the amount is suitably determined in the range of0.1 to 50,000 ppm, preferably 10 to 10,000 ppm.

The compound represented by the general formula [26] may be mixed asnecessary with an insecticide, a fungicide, other herbicide, a plantgrowth-regulating agent, a fertilizer, and the like.

The following will explain the formulation method specifically withreference to typical Formulation Examples. The kinds of compounds andadditives and their blending ratios are not restricted thereto and canbe varied in a wide range. In the following description, “parts” refersto parts by weight.

REFERENCE FORMULATION EXAMPLE 1 Wettable Powder

To 10 parts of the compound represented by the general formula [26] weremixed and pulverized 0.5 part of polyoxyethyleneoctyl phenyl ether, 0.5part of a sodium salt of β-naphthalenesulfonic acid formalin condensate,20 parts of diatomaceous earth, and 69 parts of clay, whereby a wettablepowder was obtained.

REFERENCE FORMULATION EXAMPLE 2 Flowable

Into 69 parts of water was dispersed 20 parts of a coarsely pulverizedcompound represented by the general formula [26]. Four parts of asulfate of a polyoxyethylene styrenated phenyl ether, 7 parts ofethylene glycol were added thereto, and 200 ppm of Silicone AF-118N(manufactured by Asahi Kasei Corporation) was added relative to theformulated product. The resulting mixture was stirred for 30 minutes ina high-speed stirrer and then pulverized in a wet pulverizer to obtain aflowable.

REFERENCE FORMULATION EXAMPLE 3 Emulsifiable concentrate

To 30 parts of the compound represented by the general formula [26] wereadded 60 parts of an equal volume mixture of xylene and isophorone and10 parts of a mixture of surfactants, a polyoxyethylene sorbitanalkylate, a polyoxyethylenealkyl aryl polymer, and an alkylarylsulfonate. The resulting mixture was thoroughly stirred to obtain anemulsifiable concentrate.

REFERENCE FORMULATION EXAMPLE 4 Granule

Ten parts of water was added to 10 parts of the compound represented bythe general formula [26], 80 parts of an extender where talc andbentonite were mixed in a ratio of 1:3, 5 parts of white carbon, and 5parts of a mixture of surafactants, a polyoxyethylene sorbitan alkylate,a polyoxyethylene alkylaryl polymer, and an alkyl arylsulfonate. Theresulting mixture was thoroughly kneaded to form a paste. The paste wasextruded through sieve eyes having a diameter of 0.7 mm. The extrudatewas dried and then cut into a length of 0.5 to 1 mm to obtain a granule.

The following will explain effects of the compound represented by thegeneral formula [26] with reference to Test Examples.

REFERENCE TEST EXAMPLE 1 Test for Herbicidal Effect by Paddy Field SoilTreatment

A paddy field soil was filled in a plastic pot of 100 cm² and subjectedto puddling. Then, seeds of Echinochloa oryzicola Vasing and Monochoriavaginalis var. plantaginea were sowed and water was filled in a depth of3 cm. Next day, each wettable powder produced in accordance withFormulation Example 1 were diluted with water and dropped on the watersurface. The application amount of the wettable powder was 250 g or1,000 g per 1 hectare in terms of the active ingredient. Then, breedingwas made in a greenhouse, and the herbicidal effect of the wettablepowder was examined at the 21st day after the treatment in accordancewith the standards shown in Table 13. The results are shown in Table 14.TABLE 13 Index Herbicidal effect (extent of growth inhibition) andphytotoxicity 5 A herbicidal effect or phytotoxicity of 90% or more 4 Aherbicidal effect or phytotoxicity of 70% to less than 90 3 A herbicidaleffect or phytotoxicity of 50% to less than 70% 2 A herbicidal effect orphytotoxicity of 30% to less than 50% 1 A herbicidal effect orphytotoxicity of 10% to less than 30% 0 A herbicidal effect orphytotoxicity of 0% to less than 10%

TABLE 14 Amount of active Echinochloa Monochoria Reference ingredientoryzicola vaginalis var. Example No. (g a.i./ha) Vasing plantasinea 51000 5 5 8 1000 5 5 10 250 5 5 11 250 5 5 15 1000 5 5 18 250 5 5 20 10005 5 21 1000 5 5

REFERENCE TEST EXAMPLE 2 Test for Herbicidal Effect by Field SoilTreatment

A field soil was filled in a plastic pot of 80 cm². Seeds of Echinochloacrus-galli var. crus-galli and Setaria viridis were sowed, followed bycovering with the same soil. Each wettable powder produced in accordancewith Formulation Example 1 was diluted with water and sprayed uniformlyon the soil surface using a small sprayer, in an amount of 1,000 litersper 1 hectare so that the amount of each active ingredient became 250 gor 1,000 g per 1 hectare. Then, breeding was made in a greenhouse, andthe herbicidal effect was investigated on the 21st day from thetreatment in accordance with the standards shown in Table 13. Theresults are shown in Table 15. TABLE 15 Amount of active EchinochloaReference ingredient crus-galli var. Setaria Example No. (g a.i./ha)crus-galli viridis 3 1000 5 5 4 1000 5 5 5 1000 5 5 8 1000 5 5 15 1000 55 17 1000 5 5 20 250 5 5 24 250 5 5

REFERENCE TEST EXAMPLE 3 Test for Herbicidal Effect by Field FoliageTreatment

A sand was filled in a plastic pot of 80 cm². Seeds of Echinochloacrus-galli var. crus-galli and Setaria viridis were sowed. Breeding wasmade in a greenhouse for 2 weeks. Each Wettable powder produced inaccordance with Formulation Example 1 was diluted with water and sprayedon the whole foliage of plants from above the plants using a smallsprayer in an amount of 1,000 liters per 1 hectare so that the amount ofthe active ingredient became 250 g or 1,000 g per 1 hectare. Then,breeding was made in the greenhouse, and the herbicidal effect wasinvestigated on the 14th day from the treatment in accordance with thestandards shown in Table 13. The results are shown in Table 16. TABLE 16Amount of active Echinochloa Reference ingredient crus-galli var.Setaria Example No. (g a.i./ha) crus-galli viridis 3 1000 5 5 6 250 5 47 250 5 4 9 250 5 4 13 1000 5 4 14 1000 5 4 23 250 5 4 24 250 5 4

INDUSTRIAL APPLICABILITY

According to the present invention, there is provided pyrazolederivatives represented by the general formula [I] or salts thereof,which are useful as production intermediates for isoxazoline derivativeshaving an excellent herbicidal action (described in Japanese PatentLaid-Open No. 308857/2002). The use of the inventive compounds asproduction intermediates enables a convenient production of theisoxazoline derivatives having an excellent herbicidal action anddescribed in Japanese Patent Laid-Open No. 308857/2002 with shortersteps (less number of steps) in good total yields. Therefore, theinventive compounds are highly valuable.

1. A pyrazole derivative represented by the general formula [I] or asalt thereof:

wherein R¹ represents a C1 to C6 alkyl group, R² represents a C1 to C3haloalkyl group, R³ represents a hydrogen atom, a C1 to C3 alkyl groupwhich may be substituted with one or more substituents selected from thefollowing substituent group α, or a formyl group, R⁴ represents ahydrogen atom or a C1 to C3 haloalkyl group, provided that R⁴ representsa C1 to C3 haloalkyl group in the case that R³ is a hydrogen or a formylgroup and R⁴ is a hydrogen group or a C1 to C3 haloalkyl group in thecase that R³ is a C1 to C3 alkyl group which may be substituted with oneor more substituents selected from the following substituent group α;“Substituent group α” halogen atoms, —SH group, —SC(═NH)NH₂ group
 2. Thepyrazole derivative or salt thereof according to claim 1, wherein R⁴ isa C1 to C3 haloalkyl group.
 3. The pyrazole derivative or salt thereofaccording to claim 1, wherein R³ is a C1 to C3 alkyl group and R⁴ is ahydrogen atom.
 4. The pyrazole derivative or salt thereof according toclaim 1, wherein R³ is a methyl group which may be substituted with oneor more substituents selected from the substituent group α.
 5. Thepyrazole derivative or salt thereof according to claim 1, wherein R³ isa methyl group.
 6. A process for producing a pyrazole derivativerepresented by the general formula [3], comprising a step of reacting acompound represented by the general formula [1] with a compoundrepresented by the general formula [2]:

wherein R¹ and R² represent the same meanings as mentioned above, R⁵represents a C1 to C3 alkyl group, a phenyl group which may besubstituted, or a benzyl group which may be substituted, and R⁶represents a C1 to C3 alkyl group.
 7. A process for producing a pyrazolederivative represented by the general formula [6], comprising a step ofreacting a compound represented by the general formula [4] with acompound represented by the general formula [5] in the presence of abase:

wherein R¹, R², R⁴, and R⁶ represent the same meanings as mentionedabove, and L¹ is a leaving group which is more reactive than a halogenatom remaining after haloalkylation and represents a halogen atom, a C1to C3 alkylsulfonyloxy group, a C1 to C3 haloalkylsulfonyloxy group, aphenylsulfonyloxy group which may be substituted, or a benzylsulfonyloxygroup which may be substituted, and the like.
 8. A process for producinga pyrazole derivative represented by the general formula [6], comprisinga step of reacting a compound represented by the general formula [4]with triphenylphosphine, a compound represented by the general formula[7], and an azo compound [8]:

wherein R¹, R², R⁴, and R⁶ represent the same meanings as mentionedabove.
 9. A process for producing a pyrazole derivative represented bythe general formula [10], comprising a step of reacting a compoundrepresented by the general formula [9] with a halogenating agent:

wherein R¹, R², and R⁴ represent the same meanings as mentioned above,R⁷ and R⁸ each represents a hydrogen atom or a C1 to C2 alkyl group, andX is a halogen atom.
 10. A process for producing a pyrazole derivativerepresented by the general formula [12], comprising a step of reacting acompound represented by the general formula [10] with a compoundrepresented by the general formula [11]:

wherein R¹, R², R⁴, R⁷, R⁸, and X represent the same meanings asmentioned above.
 11. The process for producing a pyrazole derivativerepresented by the general formula [13] according to claim 10, whereinthe compound represented by the general formula [12] according to theabove (10) is hydrolyzed.
 12. The process for producing a pyrazolederivative represented by the general formula [13] according to claim10, wherein the compound represented by the general formula [10]according to the above (10) is reacted with a sulfide.
 13. A process forproducing a pyrazole derivative represented by the general formula [15],comprising a step of formylating a compound represented by the generalformula [14]:

wherein R¹ and R² represent the same meanings as mentioned above.
 14. Aprocess for producing a pyrazole derivative represented by the generalformula [17], comprising a step of reacting a compound represented bythe general formula [16] with a compound represented by the generalformula [5] in the presence of a base:

wherein R¹, R², R⁴, and L¹ represent the same meanings as mentionedabove.
 15. A process for producing a pyrazole derivative represented bythe general formula [19], comprising a step of halomethylating acompound represented by the general formula [18]:

wherein R¹, R², R⁴, and X represent the same meanings as mentionedabove.